Efficacy of a medication adherence enhancing intervention in transplantation: The MAESTRO-Tx trial.
BACKGROUND
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).


CONCLUSIONS
Our intervention was efficacious in improving adherence and sustainable. Further research should investigate clinical impact, cost-effectiveness, and scalability.
Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium; Institute of Nursing Science, University of Basel, Basel, Switzerland. Electronic address: fabienne.dobbels@kuleuven.be.
Fabienne
F
Dobbels
Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium.
Leentje
L
De Bleser
Institute of Nursing Science, University of Basel, Basel, Switzerland.
Lut
L
Berben
AARDEX Group, a WestRock Healthcare Company, Visé, Belgium.
Paulus
P
Kristanto
Lung Transplant Program, University Hospitals of Leuven, Leuven, Belgium.
Lieven
L
Dupont
Liver Transplant Program, University Hospitals of Leuven, Leuven, Belgium.
Frederik
F
Nevens
Heart Transplant Program, University Hospitals of Leuven, Leuven, Belgium.
Johan
J
Vanhaecke
Lung Transplant Program, University Hospitals of Leuven, Leuven, Belgium.
Geert
G
Verleden
Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium; Institute of Nursing Science, University of Basel, Basel, Switzerland.
Sabina
S
De Geest
D000328:Adult; D000368:Aged; D001530:Belgium; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D016040:Lung Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care / Q000379:methods; D018570:Risk Assessment; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D014181:Transplantation Immunology / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult; D016903:Drug Monitoring
D007166:Immunosuppressive Agents; D016559:Tacrolimus
heart transplantation; liver transplantation; lung transplantation; medication adherence; randomized controlled trial