The Use of ACE Inhibitors in the Early Renal Post-transplant Period

Study Overview
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Brief Summary
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Chronic allograft nephropathy (CAN) is the leading cause of longterm renal transplant loss. Angiotensin-II may play a role in the development and progression of CAN. Angiotensin converting enzyme inhibitors (ACEI) comprise a drug class that inhibit the effects of angiotensin-II. However these drugs have been reported to cause elevated potassium and creatinine levels in some renal transplant patients. Yet, there are now several retrospective reports of long term benefits of improved renal function and graft survival in renal transplant recipients. There have been no reports of prospective randomized controlled trials of ACEI in renal transplant patients in the early post transplant period. The purpose of the present study is to assess the safety of enalapril, a drug in the ACEI class, when started 1-3 month post transplant. This is a double-blinded, randomized control trial of enalapril vs. placebo in new renal transplant patients with serum creatinine values no higher than 2.5mg/dl and normal serum potassium levels. The study drug will be administered for 6 months. Patients will be monitored in the renal transplant clinic every 1-4 weeks according to routine protocol. Clinical end-points will be occurence of potassium >5.9mEQ/L or sustained increase in serum creatinine >30% from baseline.

Detailed Description
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All new renal transplant recipients with functioning allografts and serum creatinine less than 2.6 mg/dl within the first 3 month post transplant would be eligible for this study of the safety of enalapril 5 mg vs placebo. Patients with serum potassium persistently over 5.5 mEQ/L would be excluded. This is a double-blinded randomized control study. End-points of the study are a persistent rise in serum creatinine of >30% from baseline not otherwise explained by clinical evaluation, and persistent serum potassium >5.9mEQ/L. Study duration is 6 month. At the end of the study patients will be continued on ACEI if clinically stable

Official Title
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The Use of ACE Inhibitors in the Early Renal Post-transplant Period

Conditions
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Renal Transplant

Intervention / Treatment
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* Drug: enalapril
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New adult renal transplant recipients with good renal function defined as serum creatinine less than 2.6 mg/dl, Normal serum potassium levels, No contraindication to ACE inhibitor use Exclusion Criteria: Renal transplant patients with persistent serum creatinine levels over 2.5 mg/dl Hyperkalemia with serum potassium levels over 5.5 mEQ/dl History of allergic reaction to ACE inhibitors or angiotensin receptor blockers Pregnancy

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: enalapril<br> | Drug: enalapril<br>* 5mg enalapril daily for 6 months<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 5mg enalapril-matching placebo daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum creatinine levels assessed at 6 months | Creatinine is a waste product that comes from the normal wear and tear on muscles of the body. It is excreted through the kidneys. High serum creatinine levels in the blood indicate that the kidneys aren't functioning properly. Increase in serum creatinine of 30% would be a safety concern and requires clinical management. | Baseline and 6 months | 
| Changes in potassium levels assessed at 6 months | Potassium is a chemical that is critical to the function of nerve and muscle cells, including those in your heart. Potassium levels must be kept within a very narrow concentration range. High Potassium levels are a sign of worsening kidney function. An occurence of serum potassium greater than 5.9 mEq/L is a safety concern and requires clinical management. | Baseline and 6 months | 
| Decrease in estimated glomerular filtration rate (eGFR) assessed at 6 months | eGFR is a number based on your blood test for creatinine, a waste product in your blood.It tells how well your kidneys are working. A normal eGFR is 60 or more. A 25 percent decrease in eGFR indicates that the kidneys may not be working well. This is a safety concern and requires clinical management. | Baseline and 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cough due to drug intolerance assessed at 6 months | Cough experienced because of inability to tolerate the adverse effects of the medication | Baseline and 6 months | 
| abdominal pain due to drug intolerance assessed at 6 months | Abdominal pain experienced because of inability to tolerate the adverse effects of the medication | Baseline and 6 months | 
| Erythrocytosis assessed at 6 months | Erythrocytosis is a condition in which your body makes too many red blood cells (RBCs). Too many red blood cells can make your blood thicker than normal and lead to blood clots and other complications. | Baseline and 6 months | 
| Leukopenia assessed at 6 months | Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection. | Baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal transplant, ACE inhibitor