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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00930241
Recruitment Status : Terminated (logistic reasons (insufficient funding, technical problems with MEMS))
First Posted : June 30, 2009
Last Update Posted : August 22, 2018
Information provided by (Responsible Party):
Hannover Medical School

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.

Condition or disease Intervention/treatment Phase
Lung Transplantation Drug: Advagraf® Drug: Prograf® Phase 3

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)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : July 2009
Actual Primary Completion Date : July 2012
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
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)

Primary Outcome Measures :
  1. 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 ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00930241

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Department of Respiratory Medicine, Medizinische Hochschule Hannover
Hannover, Germany, 30625
Hannover Medical School, Dept. of Respiratory Medicine
Hannover, Germany, 30625
Hannover Medical School
Hannover, Germany, 30625
Sponsors and Collaborators
Hannover Medical School
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Principal Investigator: Jens T Gottlieb, M.D. Hannover Medical School
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Responsible Party: Hannover Medical School Identifier: NCT00930241    
Other Study ID Numbers: 5281M mono
First Posted: June 30, 2009    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018
Keywords provided by Hannover Medical School:
Lung Transplantation
Deterioration of graft function
Additional relevant MeSH terms:
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Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action