Efficacy of a medication adherence enhancing intervention in transplantation: The MAESTRO-Tx trial
Well-designed randomized controlled trials (RCTs) testing efficacy of post-transplant medication adherence enhancing interventions and clinical outcomes are scarce.
METHODS:This randomized controlled trial enrolled adult heart, liver, and lung transplant recipients who were >1 year post-transplant and on tacrolimus twice daily (convenience sample) (visit 1). After a 3-month run-in period, patients were randomly assigned 1:1 to intervention group (IG) or control group (CG) (visit 2), followed by a 6-month intervention (visits 2-4) and a 6-month adherence follow-up period (visit 5). All patients used electronic monitoring for 15 months for adherence measurement, generating a daily binary adherence score per patient. Post-intervention 5-year clinical event-free survival (mortality or retransplantation) was evaluated. The IG received staged multicomponent tailored behavioral interventions (visits 2-4) building on social cognitive theory and trans-theoretical model (e.g., electronic monitoring feedback, motivational interviewing). The CG received usual care and attended visits 1-5 only. Intention-to-treat analysis used generalized estimating equation modeling and Kaplan-Meier survival analysis.
RESULTS:Of 247 patients, 205 were randomly assigned (103 IG, 102 CG). At baseline, average daily proportions of patients with correct dosing (82.6% IG, 78.4% CG) and timing adherence (75.8% IG, 72.2% CG) were comparable. The IG had a 16% higher dosing adherence post-intervention (95.1% IG, 79.1% CG; p < 0.001), resulting in odds of adherence being 5 times higher in the IG than in the CG (odds ratio 5.17, 95% confidence interval 2.86-9.38). This effect was sustained at end of follow-up (similar results for timing adherence). In the IG, 5-year clinical event-free survival was 82.5% vs 72.5% in the CG (p = 0.18).
CONCLUSION:Our intervention was efficacious in improving adherence and sustainable. Further research should investigate clinical impact, cost-effectiveness, and scalability.
CET Conclusion
| Reviewer: | Mr Simon Knight, Centre for Evidence in Transplantation, The Royal College of Surgeons of England. |
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| Conclusion: | This interesting study investigated the effect of a multicomponent behavioural intervention in improving drug adherence in heart, liver and lung transplant recipients. Patients randomised to the intervention arm demonstrated significantly improved dosing and timing adherence compared to controls. This effect was maintained for 6 months. There was a trend towards improved clinical event-free survival, although this did not reach significance (82.5% vs. 72.5%). The study is well-designed, with a clearly described intervention, randomisation stratified by organ type, and blinding of outcome assessment. It should be noted, however, that 10.9% patients did not consent to the study, and a further 17% dropped out before intervention, which may mean that the sample receiving the intervention are not typical of the population as a whole. Future studies should assess similar interventions in the kidney transplant population, and further investigate the longevity of the effect. |
Expert Review
| Reviewer: | Dr Patrizia Burra, Multivisceral Transplant Unit, Padova University Hospital, Padova, Italy. |
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| Conflicts of Interest: | No |
| Clinical Impact Rating | 4 |
| Review: | The key findings of this RCT are related to the efficacy of an adherence enhancing intervention in 205 transplant recipients. The Authors have found that the intervention group reported 16% higher adherence post-intervention compared to controls, which was 5 times higher. Moreover, in the intervention group, 5-year clinical event-free survival was 82.5% vs. 72.5% in the control group. The design of the study is well defined; the Authors have used a clear taxonomy in order to specify the assessed component of adherence, and to describe the interventions. The methodology is essential in this kind of study to allow the possibility of replicating the intervention. There are only few studies and RCTs that investigate the role of adherence enhancing interventions (and some of these have limitations due to a small sample size or a not well-defined framework). However, we are still missing the long-term assessment of adherence. The Authors have evaluated transplant recipients 6 months after interventions but as they stated, only a longer follow-up would improve the assessment of the intervention's efficacy. This may help to understand if some reinforcement measures need to be implemented after the intervention period. |
Methodological quality
| Jadad score | 3 |
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| Allocation concealment | YES |
| Data analysis | INTENTION TO TREAT |
| Research notes | Dr Dobbels confirmed permuted-block randomization (blocks of 4) was utilised, stratified per organ. |
Study Details
| Aims: | To test the efficacy and sustainability of a 6-month post-transplant medication adherence enhancing intervention among adult heart, liver, and lung transplant recipients. |
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| Interventions: | Participants were randomly assigned to either the intervention group or control group. Those in the intervention group received a theory-based multicomponent staged tailored medication adherence intervention using selected behavioural change techniques derived from the social-cognitive and trans-theoretical model, while the control group received usual care. |
| Participants: | 205 patients who had received their first single heart, liver or lung transplant at least one year prior to enrolment, aged ≥ 18 years and treated with tacrolimus twice-daily. |
| Outcomes: | The primary outcomes measured were medication adherence including correct dosing and timing adherence, and Basel Assessment of Adherence to Immunosuppressive medications (BAASIS) score. The seondary measured outcome was 5-year clinical event-free survival. |
| Follow Up: | 5 years |
Metadata
| Funding: | Non-industry funding |
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| Publication type: | Comparative Study, Randomized Controlled Trial, Randomised Controlled Trial |
| Organ: | Various; Heart; Liver; Lung |
| Language: | English |
| Author email: | fabienne.dobbels@kuleuven.be |
| MeSH terms: | Adult; Aged; Belgium; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Graft Survival; Heart Transplantation; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Liver Transplantation; Lung Transplantation; Male; Medication Adherence; Middle Aged; Postoperative Care; Risk Assessment; Survival Rate; Tacrolimus; Time Factors; Transplantation Immunology; Treatment Outcome; Young Adult |