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

Prospective Randomized Trial to Compare a Twice Daily to a Once Daily Administration of the Tacrolimus in Lung Transplanted Patients

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

Study Overview

• Status: Terminated
• Conditions: Lung Transplantation
• Intervention / Treatment: Drug: Advagraf®; Drug: Prograf®

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)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hannover, Germany, 30625
    • Hannover Medical School
  • Hannover, Germany, 30625
    • Department of Respiratory Medicine, Medizinische Hochschule Hannover
  • Hannover, Germany, 30625
    • Hannover Medical School, Dept. of Respiratory Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Deterioration of graft function (FEV1) before and at month 12 after conversion	6 months
Number of drug holidays (intake of less than 50% of prescribed doses in 24 hours) measured electronically	6 months

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Investigators: Principal Investigator: Jens T Gottlieb, M.D., Hannover Medical School

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: June 29, 2009
• First Submitted That Met QC Criteria: June 29, 2009
• First Posted (Estimate): June 30, 2009

Study Record Updates

• Last Update Posted (Actual): August 22, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Tacrolimus; Lung Transplantation; Deterioration of graft function
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 5281M mono