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Transplant Trial Watch

The Transplant Trial Watch provides a monthly overview of the 10 most important new clinical trials in organ transplantation, selected and reviewed by the Peter Morris Centre for Evidence in Transplantation (Oxford University)

May 2021

Heart


  1. Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial
    Journal of Heart & Lung Transplantation. 2021;40(5):359-367

    Study Details

    Aims: This study aimed to investigate whether intravenous iron therapy led to improvement in peak oxygen consumption in cardiac transplant patients.
    Interventions: Participants were randomly assigned to either the intravenous ferric derisomaltose group or the placebo group.
    Participants: 52 heart transplant patients.
    Outcomes: The primary endpoint was peak oxygen consumption. The secondary outcomes included iron deficiency (absolute or functional), muscle strength, quality of life, cardiac function and safety.

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    The double-blind, randomised controlled trial tested the hypothesis that a single intravenous infusion of ferric derisomaltose would improve peak oxygen consumption in heart transplant recipients with iron deficiency who were at least one year posttransplant. Patients were randomised according to a computer-generated randomisation list and allocation was concealed by using opaque, sealed envelopes. Double-blinding was ensured by using the following procedure: a nurse not otherwise involved in the study prepared and administered the infusion solution, the patient was blindfolded, and the injection site, syringes, and intravenous lines were all covered. The sample size calculation was based on the primary outcome peak oxygen consumption and indicated that 102 patients would provide 80% power, taking into account dropouts. Peak oxygen consumption did not differ at the 6-month follow-up. The change in health-related quality of life was greater in the intervention arm (EQ-5D-3L) compared to placebo, however this was not the case for the physical component of the SF-36. A pre-specified subgroup analysis showed that patients with very low iron at baseline (ferritin <30 mg/liter, n=12) did show an improvement in peak oxygen consumption.

    Abstract

    AIMS: Heart transplant recipients have reduced exercise capacity despite preserved graft function. The IronIC trial was designed to test the hypothesis that intravenous iron therapy would improve peak oxygen consumption in these patients. METHODS AND RESULTS This randomized, placebo-controlled, double-blind trial was performed at our national center for heart transplantation. One hundred and 2 heart transplant recipients with a serum ferritin <100 microg/liter or 100 to 300 microg/liter, in combination with transferrin saturation of <20%, and hemoglobin level >100 g/liter were enrolled >=1 year after transplantation. A cardiopulmonary exercise test was performed before administration of the study drug and at 6 months follow-up. The primary endpoint was peak oxygen consumption. Key secondary outcomes included iron status, handgrip strength, quality of life, and safety. Fifty-two patients were randomized to receive ferric derisomaltose 20 mg/kg, and 50 to placebo. The between-group difference in baseline-adjusted peak oxygen consumption was 0.3 ml/kg/min (95% confidence interval -0.9 to 1.4, p=0.66). In patients with a baseline ferritin <30 microg/liter, peak oxygen consumption was significantly higher in the ferric derisomaltose arm. At 6 months, iron stores were restored in 86% of the patients receiving ferric derisomaltose vs 20% in patients receiving placebo (p < 0.001). Quality of life was significantly better in patients receiving ferric derisomaltose. Twenty-seven adverse events occurred in the intravenous iron group vs 30 in the placebo group (p=0.39). CONCLUSION Intravenous iron treatment did not improve peak oxygen consumption in heart transplant recipients with ferritin <100 microg/liter or 100 to 300 microg/liter in combination with transferrin saturation <20%. TRIAL REGISTRATION NUMBER http//www.clinicaltrials.gov identifier NCT03662789.

Kidney


  1. Every two-month belatacept maintenance therapy in kidney transplant recipients greater than one-year post-transplant: a randomized, non-inferiority trial
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2021;[record in progress]

    Study Details

    Aims: The aim of this study was to determine whether the administration of belatacept every two months was noninferior to standard monthly dosing in kidney transplant patients with low immunologic risk.
    Interventions: Participants were randomly assigned to receive belatacept therapy every month (q1m) or every two months (q2m).
    Participants: 166 renal transplant patients.
    Outcomes: The primary endpoint was the assessment of estimated glomerular filtration rate (eGFR) at 12 months. The secondary endpoints included patient death, graft loss, rejection, the incidence of infections, and formation of donor-specific antibodies (DSA).

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    This well-designed study randomised stable, low risk renal transplant recipients > 1 year post-transplant to once-monthly or once every 2 month belatacept. The study was conducted on a non-inferiority basis, and the authors found that 2-monthly belatacept resulted in non-inferior 12-month eGFR supporting less frequent dosing in these patients. There were numerically more acute rejection episodes in the 2-monthly arm, which the authors ascribe to non-adherent behavior. There is the possibility of detection bias – for safety reasons, the patients in the 2-monthly arm had more frequent lab tests for the 4 months after switching regimens. Nonetheless, this perhaps highlights the importance of careful assessment of patient adherence when considering a regimen such as this, as the potential consequence of missed doses will be greater than more frequent dosing.

    Abstract

    Belatacept results in improved kidney transplant outcomes, but utilization has been limited by logistical barriers related to monthly (q1m) intravenous infusions. Every 2-month (q2m) belatacept has potential to increase utilization, therefore we conducted a randomized non-inferiority trial in low immunologic risk renal transplant recipients greater than one-year post-transplant. Patients on belatacept were randomly assigned to q1m or q2m therapy. The primary objective was a non-inferiority comparison of renal function (eGFR) at 12 months with a non-inferiority margin (NIM) of 6.0 ml/min/1.73m(2) . 166 participants were randomized to q1m (n=82) or q2m (n=84) belatacept, 163 patients received treatment, and 76 q1m and 77 q2m subjects completed the 12-month study period. Every 2-month belatacept was non-inferior to q1m, as the difference in mean eGFR adjusted for baseline renal function did not exceed the NIM. Two-month dosing was safe and well tolerated, with no patient deaths or graft losses. Four rejection episodes and three cases of donor-specific antibodies (DSA) occurred amongst q2m subjects; however, only one rejection and one instance of DSA was observed in subjects adherent to the study protocol. Every two-month belatacept therapy may facilitate long-term utilization of costimulation blockade, but future multicenter studies with longer-term follow-up will further elucidate immunologic risk.
  2. Range and Consistency of Infection Outcomes Reported in Trials Conducted in Kidney Transplant Recipients: a Systematic Review
    Transplantation. 2021;[record in progress]

    Study Details

    Aims: The aim of this study was to evaluate the scope and consistency of reporting of infection outcomes in contemporary randomised controlled trials (RCTs) in renal transplant recipients.
    Interventions: A literature search was conducted on the Cochrane Kidney and Transplant Specialised Register. Study selection was carried out by two independent reviewers. The methodological quality of the included studies was not assessed.
    Participants: 102 trials were included in the review.
    Outcomes: The main outcomes of interest were infection outcomes and outcome measures used in the included trials.

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    This review investigates the consistency of reporting of infection outcomes in RCTs in kidney transplantation. The authors included 102 trials, finding 216 unique infection outcomes. Systematic infection and CMV were the most frequently reported outcomes. Reporting of infection outcomes was very variable, with different definitions and timepoints commonly used. Methodology is generally good with clear inclusion criteria and outcome definitions. Data extraction was only completed by a single reviewer with no checking for quality/consistency. No attempt is made to assess the quality of the included studies, although this is perhaps less relevant in a review of this type. The review highlights the need for greater consistency in reporting trial outcomes in this area, and the authors rightly suggest that a core outcome set might be of use. Greater consistency would facilitate comparisons between trials and future systematic review.

    Abstract

    BACKGROUND Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients. METHODS A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients were identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed. RESULTS From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1 to 9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome was systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1 to 11 time points per trial. CONCLUSIONS Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability and usefulness of trial evidence.Supplemental Visual Abstract; http://links.lww.com/TP/C169.
  3. Prediction of Kidney Allograft Discard Before Procurement: The Kidney Discard Risk Index
    Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2021;19(3):204-211

    Study Details

    Aims: The aim of this study was to establish predictors of kidney discard and to derive a kidney discard risk index (KDSRI) on the basis of these factors.
    Interventions: The study population was randomized to the training set and the validation set.
    Participants: 102,246 potential renal allograft donors.
    Outcomes: The primary outcome was renal allograft discard.

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    This paper attempts to derive a risk index for kidney allograft discard using OPTN data from the US. The authors randomly split a cohort of 102,246 kidney offers into training and validation sets and used logistic regression to create an index to predict discard based upon factor available prior to procurement. The final model shows a C-statistic of 0.89, suggesting good performance in this cohort. The three most predictive factors for discard were age, serum creatinine and hepatitis C antibody status. The authors suggest that the risk index couple be used to identify organs at high risk of discard as a basis for interventions or allocation policies to improve utilization. One interesting aspect of this study is that the authors also developed machine learning models based on the same input variables and demonstrated that the logistic regression model achieved similar performance to machine learning approaches whilst maintaining better transparency and explainability. Clearly, the model is only validated in the US allocation system and may not have the same predictive performance in other settings – further research should explore generalizability.

    Abstract

    OBJECTIVES There is an 18.9% discard rate among kidney allografts. Here, we aimed to determine predictors of kidney discard and construct an index to identify high-probability discard kidney allografts prior to procurement. MATERIALS AND METHODS A total of 102 246 potential kidney allograft donors from the Organ Procurement and Transplantation Network database were used in this analysis. The cohort was randomized into 2 groups. The training set included 67% of the cohort and was used to derive a predictive index for discard that comprised 21 factors identified by univariate and multivariate logistic regression analysis. The validation set included 33% and was used to internally validate the kidney discard risk index. RESULTS In 77.3% of donors, at least 1 kidney was used for transplant, whereas in 22.7% of donors, both kidneys were discarded. The kidney discard risk index was highly predictive of discard with a C statistic of 0.89 (0.88-0.89). The bottom 10th percentile had a discard rate of 0.73%, whereas the top 10th percentile had a discard rate of 83.65%. The 3 most predictive factors for discard were age, creatinine level, and hepatitis C antibody status. CONCLUSIONS We identified 21 factors predictive of discard prior to donor procurement and used these to develop a kidney discard risk index with a C statistic of 0.89.
  4. Association between medication adherence and intrapatient variability in tacrolimus concentration among stable kidney transplant recipients
    Scientific Reports. 2021;11(1):5397

    Study Details

    Aims: This study is a post-hoc analysis of a randomised controlled trial (RCT) evaluating the effectiveness of a mobile medication manager application in improving medication adherence in renal transplant patients. The aim of this study was to investigate the link between intrapatient variability (IPV) of tacrolimus concentrations and adherence to medication among the renal transplant patients included in the RCT.
    Interventions: Participants were randomised to either the mobile group or the control group.
    Participants: 92 renal transplant recipients.
    Outcomes: The main outcome of interest was the assessment of IPV and the time in therapeutic range (TTR) in the adherent versus the nonadherent group. Additionally, the study measured the incidence of de novo donor-specific antibodies (dnDSA) and estimated glomerular filtration rate (eGFR) between the groups.

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    Previous studies have shown an association between intrapatient variability in tacrolimus levels (IPV) and graft outcomes following kidney transplantation. Studies have worked on the assumption that IPV relates to poor adherence, with missed doses and suboptimal dose timing resulting in increased variability. This study investigates the relationship between IPV and adherence in a post-hoc analysis of an RCT using electronic medication monitoring and self-reported adherence. The authors found no relationship between any of the adherence measures used and tacrolimus IPV, suggesting that the use of IPV as a surrogate for compliance is not justified. It should be noted that the population included in this study had a low IPV overall, and previous studies have suggested that the relationship between IPV and adverse outcomes is seen at higher levels than typically seen in patients in the present study. Therefore, selection of a more poorly adherent population at baseline may have led to different findings.

    Abstract

    This study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with >= 5 months of medication event monitoring system (MEMS) use and >= 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6-25.5%] and 16.0% [11.5-23.5%], respectively, P = .602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, rho = - 0.067, P = .527; dosing adherence, rho = - 0.098, P = .352; timing adherence, rho = - 0.113, P = .284). Similarly, adherence measured by self-report did not significantly affect the IPV (P = .452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV.
  5. Association between day of the week and medication adherence among adolescent and young adult kidney transplant recipients
    American Journal of Transplantation. 2020;20(1):274-281

    Study Details

    Aims: This post-hoc analysis of the Teen Adherence in Kidney transplant Effectiveness of Intervention Trial (TAKE‐IT) aimed to investigate whether adolescent and young adult renal transplant patients had poorer medication adherence during weekends in comparison to weekdays.
    Interventions: Participants in the TAKE-IT trial were randomly assigned to either the adherence-promoting intervention group, or the control group where adherence was not discussed.
    Participants: 138 kidney transplant patients aged 11 to 24 years.
    Outcomes: The main outcomes of interest were the proportion of prescribed doses administered (taking adherence), and the proportion of prescribed doses administered within a period of 1 hour before to 2 hours after the dosing time prescribed (timing adherence).

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    This is a post-hoc analysis of the Teen Adherence in Kidney transplant Effectiveness of Intervention Trial (TAKE-IT) which showed that participants in the intervention arm had significantly greater odds of taking prescribed medications and taking medications at or near the prescribed time compared to the control group (https://www.transplantlibrary.com/article/29602631). The post-hoc analysis reviewed whether medication adherence differs by day of the week and included 138 adolescent and young adult kidney transplant recipients. Data showed that taking adherence (100% adherence) and on-time dosing (100% timing adherence) was less likely on weekends than weekdays but there was no difference by treatment group. The authors suggest that the change in routine between weekdays and weekends causes poor adherence on weekends.

    Abstract

    Disruption of usual routines may hinder adherence, increasing the risk of rejection. We aimed to compare weekend versus weekday medication adherence among adolescent and young adult kidney transplant recipients, hypothesizing poorer adherence on weekends. We examined data from the Teen Adherence in Kidney transplant Effectiveness of Intervention Trial (TAKE-IT). We assessed the 3-month run-in period (no intervention) and the 12-month intervention interval, considering a potential interaction between weekend/weekday and treatment group. Adherence was monitored using electronic pillboxes in participants 11-24 years followed in eight transplant centers in Canada and the United States. We used logistic regression with generalized estimating equations to estimate the association between weekends/weekdays and each of perfect taking (100% of prescribed doses taken) and timing (100% of prescribed doses taken on time) adherence. Taking (OR = 0.72 [95% CI 0.65-0.79]) and timing (OR = 0.66 [95% CI 0.59-0.74]) adherence were poorer on weekends than weekdays in the run-in (136 participants) and the intervention interval (taking OR = 0.74 [0.67-0.81] and timing OR = 0.71 [95% CI 0.65-0.77]). There was no interaction by treatment group (64 intervention and 74 control participants). Weekends represent a disruption of regular routines, posing a threat to adherence. Patients and families should be encouraged to develop strategies to maintain adherence when routines are disrupted. TAKE-IT registration number: Clinicaltrials.gov registration: NCT01356277 (May 17, 2011).

Liver


  1. Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial
    The New England journal of medicine. 2021;384(15):1391-1401

    Study Details

    Aims: The aim of this study was to compare the effect of hypothermic oxygenated machine perfusion with that of static cold preservation in recipients of liver transplants from donors after circulatory death.
    Interventions: Participants were randomised to either the machine-perfusion group or the control group.
    Participants: 160 liver transplant patients aged ≥ 18 years.
    Outcomes: The primary outcome was the occurrence of nonanastomotic biliary strictures during a period of 6 months following transplantation. The secondary endpoints were graft-related and general complications.

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    This is a well-conducted, multicenter randomised controlled trial (RCT) that took place across 6 transplant centres in 3 European countries, and included 160 patients. Livers from donation after circulatory death were randomised by a centralised, computerised system, with stratification for centre and recipient Primary Sclerosing Cholangitis. The livers were randomised to either static cold storage, or static cold storage followed by minimum 2 hours perfusion in the Liver Assist device from Organ Assist, which provides dual oxygenated cold perfusion. Median perfusion time in the study was short (2 hours 12 minutes) but this meant that the overall cold ischaemic time was longer in the perfused group (8 hours 44 minutes versus 6 hours 49 minutes). The study found a significant reduction in symptomatic, non-anastomotic, biliary strictures associated when livers were perfused (6% versus 18%). Importantly, radiologists were blinded to group allocation and scans were reviewed by two radiologists independently, with discrepancies reviewed by a third. There was also a significant reduction in the risk of post-reperfusion syndrome with perfused livers. There was one case of primary non-function in the control group and none in the study group. There was no significant difference in early allograft dysfunction. This well-conducted study clearly shows that a short period of oxygenated hypothermic perfusion of DCD livers can reduce the incidence of non-anastomotic biliary strictures compared to static cold storage alone, despite a longer overall period of cold storage.

    Abstract

    BACKGROUND Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited. METHODS In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications. RESULTS A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups. CONCLUSIONS Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).
  2. Refitting the Model for End-stage Liver Disease for the Eurotransplant region
    Hepatology. 2020;[record in progress]

    Study Details

    Aims: This study aimed to establish a refit model for end-stage liver disease (reMELD) score for the Eurotransplant region.
    Interventions: Patient data were randomly divided into a training set and a validation set.
    Participants: 6944 patients listed for a first liver transplant.
    Outcomes: The primary endpoint was patient death during 90 days of first active listing, including both actively listed and removed patients.

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    This is a very interesting report detailing the work done to re-fit the UNOS-MELD for the European population and using a modern cohort. All adult patients listed in an 11-year period were included (6,944), with 70% being used for training and 30% for validation. The primary outcome was death within 90 days of listing. Importantly, removed patients that died within 90 days were included in the analysis. The reweighted parameters performed significantly better in the validation cohort than the previous MELD model, resulting in greater “sickest-first” allocation.

    Abstract

    BACKGROUND The UNOS-MELD score is the basis of liver allocation in the Eurotransplant region. It was constructed 20 years ago in a small US cohort and has remained unchanged ever since. The best boundaries and coefficients were never calculated for any region outside the US. Therefore, this study refits MELD (reMELD) for the Eurotransplant region. METHODS All adult patients listed for a first LT between 01.01.2007-31.12.2018 were included. Data was randomly split in a training (70%) and validation (30%) set. In the training data, generalized additive models (GAMs) with splines were plotted for each MELD parameter. The lower and upper bound combinations with the maximum log-likelihood were chosen for the final models. The refit models were tested in the validation data with c-indices and Brier scores. Through likelihood ratio tests the refit models were compared to UNOS-MELD. The correlation between scores and survival of prioritized patients was calculated. RESULTS A total of 6,684 patients were included. Based on training data, refit parameters were capped at creatinine 0.7-2.5, bilirubin 0.3-27, INR 0.1-2.6 and sodium 120-139. ReMELD and reMELD-Na showed c-indices of 0.866 and 0.869 respectively. ReMELD-Na prioritized patients with 1.6 times higher 90-day mortality probabilities as compared to UNOS-MELD. CONCLUSION Refitting MELD resulted in new lower and upper bounds for each parameter. The predictive power of reMELD-Na was significantly higher than UNOS-MELD. ReMELD prioritized patients with higher 90-day mortality rates. Thus, reMELD(-Na) should replace UNOS-MELD for liver graft allocation in the Eurotransplant region.
  3. Clinical study of argatroban for preventing vascular thrombosis in the early period after pediatric living-related donor liver transplantation
    Pediatric Transplantation. 2020;24(2):e13654

    Study Details

    Aims: This study aimed to compare the effectiveness of heparin versus argatroban in preventing vascular thrombosis during the early period following pediatric living-related donor liver transplantation (LRDLT).
    Interventions: Participants were randomly split into either the heparin group or the argatroban group.
    Participants: 84 pediatric LRDLT patients.
    Outcomes: The outcomes of interest were antithrombin III (AT-III) activity, activated partial thromboplastin time (APTT), international normalized ratio (INR), and the incidence of vascular thrombosis and adverse reactions.

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    Thrombotic complications after liver transplantation can be catastrophic and the risk is increased in paediatric transplantation. However, the impact of this particular study on this clinical issue is limited. It is a clinical trial in paediatric liver transplantation with only 2 authors. 84 recipients were included, all of whom were receiving transplants from their parents and the primary outcome is not declared clearly. Patients were randomised to 2 arms of the study in a 3:1 ratio (heparin or argatroban), but the method of randomisation is not explained. No power calculation is presented to justify or explain the size of study, or the reason for the 3:1 group allocation and there is no description of blinding. Both heparin and argatroban were only given for the first 5 days after surgery. Antithrombin-III levels were similar between the groups but it is not clear that the study was adequately powered for this outcome. There was a significant difference in APTT, being longer with argatroban, and more thrombotic complications in the heparin group, but strong conclusions cannot be drawn from this small study with no description of randomisation or blinding.

    Abstract

    OBJECTIVE To evaluate the effect of heparin and argatroban on coagulation function and vascular thrombosis in the early period after pediatric LRDLT. METHOD Eighty-four congenital biliary atresia pediatric patients who had undergone LRDLT were studied. Patients were divided into two groups according to the method of anticoagulation (heparin or argatroban). AT-III activity, APTT, and INR of the two groups were measured in the first 5 days after LRDLT. Vascular thrombosis was investigated by Doppler ultrasound daily. RESULTS There were no significant differences in gender, age, weight, graft-recipient weight ratio, and Kasai procedure between the two groups. The AT-III activity of the two groups was low and increased gradually after surgery, with no significant difference between the two groups. There was no significant difference of APTT between the two groups immediately after and in the first day after surgery. After anticoagulation treatment, a significant difference in APTT between the two groups was observed. The incidences of vascular thrombosis were 4.76% (3/63) and 0% (0/21) in the heparin and argatroban groups, respectively, with no significant difference between the two groups. During the treatment, no serious complications such as active hemorrhage or drug allergy were observed in the two groups. CONCLUSION Argatroban is a direct anticoagulant, which is independent of AT-III activity. Argatroban might be an alternative to heparin in uncomplicated LRDLT with recovered hepatic and coagulation function.

Various


  1. Cardiac surgery outcomes in patients with antecedent kidney, liver, and pancreas transplantation: a meta-analysis
    Reviews in Cardiovascular Medicine. 2020;21(4):589-599

    Study Details

    Aims: This study aimed to compare cardiac surgery outcomes in abdominal solid organ transplant patients versus nontransplant (N-Tx) patients.
    Interventions: Electronic databases including Pubmed, SCOPUS and EMBASE were searched. Study screening and data extraction were perfomed by two reviewers. The Newcastle-Ottawa Quality Assessment Scale for cohort studies was used to assess the risk of bias.
    Participants: 5 studies were included in the review.
    Outcomes: The main endpoints included overall infectious complication rate, cardiovascular and renal events, and mortality following cardiac surgery in patients with prior solid organ transplantation versus nontransplant patients.

    CET Conclusion

    Reviewer: Centre for Evidence in Transplantation
    The systematic review compared postoperative outcomes of cardiac surgery in abdominal solid organ transplant recipients versus nontransplant patients. A comprehensive search of three bibliographic databases was conducted and two independent reviewers identified five comparative studies to include in kidney, liver, pancreas and pancreas-kidney transplantation. Two independent reviewers extracted the data and methodological quality was also assessed although it was not stated whether this was done by independent reviewers. All studies were considered to be of good methodological quality. Transplant recipients experienced worse postoperative outcomes, i.e. higher rates of wound infection, septicaemia, cardiac tamponate, kidney failure, and 5-year and 10-year mortality. No differences were found for pneumonia, post-procedural stroke rate and 30-day mortality. Heterogeneity was low for most analyses.

    Abstract

    Cardiovascular events are among the most common causes of late death in the transplant recipient (Tx) population. Moreover, major cardiac surgical procedures are more challenging and risky due to immunosuppression and the potential impact on the transplanted organ's functional capacity. We aimed to assess open cardiac surgery safety in abdominal solid organ transplant recipients, comparing the postoperative outcomes with those of nontransplant (N-Tx) patients. Electronic databases of PubMed, EMBASE, and SCOPUS were searched. The endpoints were: overall rate of infectious complications (wound infection, septicemia, pneumonia), cardiovascular and renal events (stroke, cardiac tamponade, acute kidney failure), 30-days, 5-years, and 10-years mortality post-cardiac surgery interventions in patients with and without prior solid organ transplantation. This meta-analysis included five studies. Higher rates of wound infection (Tx vs. N-Tx: OR: 2.03, 95% CI: 1.54 to 2.67, I2 = 0%), septicemia (OR: 3.91, 95% CI: 1.40 to 10.92, I2 = 0%), cardiac tamponade (OR: 1.83, 95% CI: 1.28 to 2.62, I2 = 0%) and kidney failure (OR: 1.70, 95 %CI: 1.44 to 2.02, I2 = 89%) in transplant recipients were reported. No significant differences in pneumonia occurrence (OR: 0.95, 95% CI: 0.71 to 1.27, I2 = 0%) stroke (OR: 0.89, 95% CI: 0.54 to 1.48, I2 = 78%) and 30-day mortality (OR: 1.92, 95% CI: 0.97 to 3.80, I2 = 0%) were observed. Surprisingly, 5-years (OR: 3.74, 95% CI: 2.54 to 5.49, I2 = 0%) and 10-years mortality rates were significantly lower in the N-Tx group (OR: 3.32, 95% CI: 2.35 to 4.69, I2 = 0%). Our study reveals that open cardiac surgery in transplant recipients is associated with worse postoperative outcomes and higher long-term mortality rates.