Clinical trial NCT02744872: Copenhagen Acute Renal Complications After Transplantations Study Group
Official title: Prospektivt Randomiseret Dobbeltblindt Placebo-kontrolleret Studie af, Calciumkanalblokade påbegyndt Inden Operation: Med Henblik på at Forebygge Ciclosporin Induceret Nefropati Efter Lungetransplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Disorder Related to Lung Transplantation
Keywords: lung transplantation
chronic renal insufficiency
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2016-04-20
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in glomerular filtration rate
timeFrame: week 1, 2, 3 and 12
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen Ø
country: Denmark
facility: Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
state: Copenhagen
Study officials:
affiliation: Professor
name: Bo Feldt-Rasmussen
role: PRINCIPAL_INVESTIGATOR
References: