Clinical trial NCT00930241: Twice Daily Versus Once Daily Administration of the Tacrolimus in Lung Transplantation
Official title: Prospective Randomized Trial to Compare a Twice Daily to a Once Daily Administration of the Tacrolimus in Lung Transplanted Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lung Transplantation
Keywords: Lung Transplantation
Tacrolimus
Deterioration of graft function
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
First posted: 2009-06-30
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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 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

Primary outcomes:
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: Deterioration of graft function (FEV1) before and at month 12 after conversion
timeFrame: 6 months
measure: Number of drug holidays (intake of less than 50% of prescribed doses in 24 hours) measured electronically
timeFrame: 6 months
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Department of Respiratory Medicine, Medizinische Hochschule Hannover
city: Hannover
country: Germany
facility: Hannover Medical School, Dept. of Respiratory Medicine
city: Hannover
country: Germany
facility: Hannover Medical School
Study officials:
affiliation: Hannover Medical School
name: Jens T Gottlieb, M.D.
role: PRINCIPAL_INVESTIGATOR
References: