Copenhagen Acute Renal Complications After Transplantations Study Group

Study Overview
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Brief Summary
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Lung transplanted patients experience marked decrease in renal function post transplant mainly due to cyclosporine induced renal changes. Calcium channel blockers may improve renal function in cyclosporine treated transplant recipients through their effects in avoiding cyclosporine-induced renal vasoconstriction and facilitating renal sodium output. The aim of this study is to examine if calcium channel blockade administered before lung transplantation prevent cyclosporine induced nephropathy. The design is an intention to treat randomized double blinded single center study. Patients are randomized to two groups, one that received felodipine and one that receives placebo. Study population is all patients listed for lung transplantation in Denmark in the study period. Intervention is tablet felodipine titrated to 10 mg, one daily dose in 12 weeks Primary endpoint is change in renal function as measured by glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51-Cr-EDTA) in the felodipine treated group compared with the placebo group.

Detailed Description
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Lung transplanted patients experience marked decrease in renal function post transplant mainly due to cyclosporine induced renal changes. Calcium channel blockers exert renal effects consisting mainly of renal vasodilation and facilitation of renal excretion of sodium through a direct action on renal tubules. Calcium channel blockers improve renal function in cyclosporine treated transplant recipients through their effects in avoiding cyclosporine-induced renal vasoconstriction and facilitating renal sodium output. Studies in both animal models and humans have demonstrated that calcium channel blockers maintain or reduce renal vascular resistance and preserve or enhance renal blood flow and glomerular filtration rate (GFR). The aim of this study is to examine if calcium channel blockade administered before lung transplantation prevent cyclosporine induced nephropathy. The design is an intention to treat randomized double blinded single center study. Patients are randomized to two groups, one that received felodipine and one that receives placebo. Study population is all patients listed for lung transplantation in Denmark in the study period. Sample size calculation estimated that 32 patients are needed, 16 patients in each group, with an estimated dropout incidence of 5 patients in each group. This will be able to detect an estimated 50% reduction in the decrease in measured GFR from 40 ml/min in the placebo group to 20 ml/min in treatment group, 80% power and a two-sided t-test, 5 % significance level. Intervention is tablet Felodipine titrated to 10 mg, one daily dose in 12 weeks Renal function is determined by 51-Cr-EDTA clearance measurement at times 0 before transplantation and after 1, 3 and 12 weeks. Primary endpoint is change in renal function as measured by 51-Cr-EDTA clearance in the felodipine treated group compared with the placebo group. Safety is monitored and adverse events are usually mild headache, tachycardia, leg edema, angina pectoris and hypotension.

Official Title
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Prospektivt Randomiseret Dobbeltblindt Placebo-kontrolleret Studie af, Calciumkanalblokade påbegyndt Inden Operation: Med Henblik på at Forebygge Ciclosporin Induceret Nefropati Efter Lungetransplantation

Conditions
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Disorder Related to Lung Transplantation

Intervention / Treatment
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* Drug: Felodipine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients who are undergoing lung transplantation in Denmark Exclusion Criteria: Fertile women not using contraceptives Patients allergic to calcium antagonists Patients receiving treatment with Calcium antagonist 14 days prior to transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Felodipine<br>Tablet Felodipin 10 mg x 1 daily | Drug: Felodipine<br>* Felodipine 10 mg once daily or identical placebo<br>|
| Placebo Comparator: Placebo<br>Identical placebo once daily | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glomerular filtration rate | glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51-Cr-EDTA) at week 1, 2, 3 and 12 | week 1, 2, 3 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung transplantation, chronic renal insufficiency