Twice Daily Versus Once Daily Administration of the Tacrolimus in Lung Transplantation
Information source: Hannover Medical School
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Lung Transplantation
Intervention: Advagraf® (Drug); Prograf® (Drug)
Phase: Phase 3
Status: Terminated
Sponsored by: Hannover Medical School Official(s) and/or principal investigator(s): Jens T Gottlieb, M.D., Principal Investigator, Affiliation: Hannover Medical School
Summary
This study is a prospective randomized trial to compare twice daily to once daily
administration of the basic immunosuppressive regimen in lung transplanted patients.
Clinical Details
Official title: Prospective Randomized Trial to Compare a Twice Daily to a Once Daily Administration of the Tacrolimus in Lung Transplanted Patients
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Improvement of adherence as measured by Tacrolimus trough level below the target level and dispensing of less than 50% of the prescribed doses in the last three days measured electronically before this subtherapeutic drug monitoring
Secondary outcome: Deterioration of graft function (FEV1) before and at month 12 after conversionNumber of drug holidays (intake of less than 50% of prescribed doses in 24 hours) measured electronically
Detailed description:
Prevalence data of non-compliance in solid organ transplantations fluctuate is reported in
up to 39% of transplant recipients (z. B. for lung transplantations 13 - 22%; Kugler et
al.). Non-compliance with immunosuppressive therapy is associated with an increased risk of
late-acute rejections and the development of chronic transplant dysfunction. Chronic
transplant dysfunction (bronchiolitis obliterans- syndrome-BOS) is the second most causing
for organ failure after the first year following lung transplantation and often leads to
re-transplantation or death. Preventative procedures for improving the compliance are
simplification of the dose of the immunosuppressants (a once daily dose instead of a twice
daily dose), the prescription of an immunosuppressants with less side-effects and to raise
the patient´s awareness for having the greatest responsibility for the efficacy of his
therapy. Prospective studies and metaanalysis revealed that the probability for a good
compliance can be more than doubled at once daily administration in comparison to twice
daily and the best predictor for a good compliance is an easy therapy. For this reason we
want to investigate the extent of profit for our lung transplant patients receiving once
daily basis immunosuppression in comparison to those who receive twice daily dose.
Hypothesis: Patients of the once daily administration group of the immunosuppressive
medication will have a better compliance compared to the twice daily group (as measured by
the endpoints variability and medication abstraction from the electronic devices)
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients (Pts) more than 1 year after single lung, double lung or heart/lung
transplantation
- Pts treated with cyclosporin, steroids and MMF
- Pts ≥ 18 and ≤ 70 years and
- Pts with one of the following:
- pts with recurrent acute rejections (RAR)
- two or more acute rejections in 3 months (first 3 years post Tx, 6 months (> 3
years post Tx) defined by:
- transbronchial biopsy > A1 (or A1 with clinical criteria below) nach ISHLT
(B>1R) or
- decline of FEV1 > 10 % baseline after exclusion of infection, airway
complication, effusion etc. and improvement to steroid-pulse therapy
(methylprednisolone 15 mg/kg for three days) = FEV1 improvement > 10%
compared to the last measurement before AR treatment
- Pts with steroid-resistant or ongoing acute rejections (OAR) defined by:
- transbronchial biopsy > A1 (or A1 with clinical criteria above) at least 4 weeks
following steroid-pulse therapy (methylprednisolone 15 mg/kg for three days) or
- no FEV1 improvement (< 5% baseline) at least 14 days following ACR steroid-pulse
therapy (methylprednisolone 15 mg/kg for three days) after exclusion of
infection, airway complication, effusion etc. or
- Pts with new onset of BOS (nBOS) Unexplained FEV1 < 80% of baseline after exclusion
of Infection, airway complication, effusion etc
- Pts with CyA associated side effects (e. g., hyperlipidaemia, hypertriglyceridemia,
hypertension, hirsutism, gingival hyperplasia)
Exclusion Criteria:
- Pregnant or breast feeding women
- Pts who are not using a double-barrier method of birth control
- Pts with systemic infections
- Pts with severe diarrhea, vomiting, active ulcer
- Pts with severe liver disease or liver cirrhosis
- Pts with m-Tor inhibitors
- Pts with hypersensitivity to Tacrolimus, other macrolides or other tablet ingredients
Locations and Contacts
Department of Respiratory Medicine, Medizinische Hochschule Hannover, Hannover 30625, Germany
Hannover Medical School, Hannover 30625, Germany
Hannover Medical School, Dept. of Respiratory Medicine, Hannover 30625, Germany
Additional Information
Starting date: July 2009
Last updated: March 19, 2013
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