Twice Daily Versus Once Daily Administration of the Tacrolimus in Lung Transplantation

This study has been terminated.
(logistic reasons (insufficient funding, technical problems with MEMS))
Sponsor:
Information provided by (Responsible Party):
Hannover Medical School
ClinicalTrials.gov Identifier:
NCT00930241
First received: June 29, 2009
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

This study is a prospective randomized trial to compare twice daily to once daily administration of the basic immunosuppressive regimen in lung transplanted patients.


Condition Intervention Phase
Lung Transplantation
Drug: Advagraf®
Drug: Prograf®
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Prospective Randomized Trial to Compare a Twice Daily to a Once Daily Administration of the Tacrolimus in Lung Transplanted Patients

Resource links provided by NLM:


Further study details as provided by Hannover Medical School:

Primary Outcome Measures:
  • 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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Deterioration of graft function (FEV1) before and at month 12 after conversion [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Number of drug holidays (intake of less than 50% of prescribed doses in 24 hours) measured electronically [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: July 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Advagraf
Advagraf® (one daily dose of Tacrolimus)
Drug: Advagraf®
Advagraf® (one daily dose of Tacrolimus)
Active Comparator: Prograf
Prograf® (two daily doses of Tacrolimus)
Drug: Prograf®
Prograf® (two daily doses of Tacrolimus)

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00930241

Locations
Germany
Hannover Medical School, Dept. of Respiratory Medicine
Hannover, Germany, 30625
Hannover Medical School
Hannover, Germany, 30625
Department of Respiratory Medicine, Medizinische Hochschule Hannover
Hannover, Germany, 30625
Sponsors and Collaborators
Hannover Medical School
Investigators
Principal Investigator: Jens T Gottlieb, M.D. Hannover Medical School
  More Information

No publications provided

Responsible Party: Hannover Medical School, IFB-Tx
ClinicalTrials.gov Identifier: NCT00930241     History of Changes
Other Study ID Numbers: 5281M mono
Study First Received: June 29, 2009
Last Updated: March 19, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Hannover Medical School:
Lung Transplantation
Tacrolimus
Deterioration of graft function

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 29, 2014