Renal Effects of an Angiotensin Converting Enzyme Inhibitor in Adults With Chronic Kidney Disease of Uncertain Aetiology

NCT ID: NCT01624064

Last Updated: 2012-06-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2013-10-31

Brief Summary

Enalapril would significantly reduce progression of renal disease in patients with Chronic Kidney Disease of Uncertain aetiology.

Detailed Description

End Stage Kidney Disease (ESKD) results in reduced life expectancy, quality of life and increased consumption of health care resources. Chronic Kidney Disease of Uncertain aetiology (CKDu) is being increasingly recognized in the North Central Region of Sri Lanka and in certain regions over 25% (unpublished data) of general population is suspected as suffering from CKDu. The number of patients who reach ESKD that requires hemodialysis or transplantation is increasing, highlighting the need to find strategies that slow progression of kidney disease. The need for these strategies is even more critical in Sri Lanka where dialysis in not a preferred treatment option. Treatment strategies should be readily accessible and cheap.

The importance of proteinuria as a significant risk factor for ESKD is well recognized, and treatment that is targeted at reducing proteinuria has been shown to reduce progression of renal disease. The Renin - Angiotensin - Aldosterone - System (RAAS) is directly involved in the regulation of blood pressure, fluid volume, and vascular response to injury and inflammation. The inappropriate activation of this system causes hypertension, fluid retention, and inflammatory, thrombotic, and atherogenic effects that may contribute to end-organ damage in the long term. Angiotensin II mediates hemodynamic effects as well as inflammation and fibrosis in the kidney, heart, and vasculature.

Numerous clinical trials have established that interruption of the RAAS cascade with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is beneficial in slowing progression of renal disease. Reduction of BP lowers proteinuria, but the use of an ACEI or an ARB reduces both proteinuria and the rate of deterioration of renal function beyond those seen with equivalent BP reduction from conventional antihypertensive agents. However, the use of these agents has limitations, with significant numbers of treated patients still demonstrating progressive renal disease. RAAS blockers have been shown to blunt the progression of advanced kidney disease. However the long-term renal effect of these agents in early renal disease is not well demonstrated. In fact the trials which showed benefits with RAAS blockers did show in glomerular disease and evidence is not so strong in tubulo-interstitial disease. The benefits of RAS inhibition seem to depend on the degree of proteinuria at baseline. It is marginal in those with low grade proteinuria.

In most forms of proteinuric chronic renal disease, glomerular filtration rate continues to decline even when the initial insult has been removed. The cause of CKDu is still unknown. CKDu is a tubulo-interstitial disease with low grade proteinuria. We believe that the place of ACEI for secondary prevention of CKDu progression needs investigation

Conditions

Renal Insufficiency, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Enalapril, Proteinuria < 1g/day

Group Type: ACTIVE_COMPARATOR

Enalapril

Intervention Type: DRUG

2.5-20 mg/day

Calcium, Proteinuria < 1g/day

Group Type: PLACEBO_COMPARATOR

Calcium Supplement

Intervention Type: DRUG

Calcium 2.5-20 mg/day

Enalapril, Proteinuria > 1g/day

Group Type: ACTIVE_COMPARATOR

Enalapril

Intervention Type: DRUG

2.5-20 mg/day

Calcium, Proteinuria > 1g/day

Group Type: PLACEBO_COMPARATOR

Calcium Supplement

Intervention Type: DRUG

Calcium 2.5-20 mg/day

Interventions

Enalapril

2.5-20 mg/day

Intervention Type: DRUG

Calcium Supplement

Calcium 2.5-20 mg/day

Intervention Type: DRUG

Other Intervention Names

Angiotensin Converting Enzyme Inhibitor; Calcium lactate

Eligibility Criteria

Inclusion Criteria

• Males and females between 18-70 years of age
• CKDu Grade 1, 2, 3
• No contraindication for treatment with ACEI
• Informed consent given

Exclusion Criteria

• Grade 4 CKDu
• Other chronic diseases
• Evidence or suspicion of non renal secondary hypertension
• Diabetes type 1 or 2
• Evidence or suspicion of renovascular disease, obstructive uropathy, or other renal disease
• Treatment with corticosteroids, non-steroidal anti-inflammatory drugs, or immune-suppressive drugs
• Acute myocardial infarction or cerebrovascular accident in the previous 6 months
• Severe uncontrolled hypertension (diastolic blood pressure ≥115 and/or systolic blood pressure ≥220 mm Hg)
• Suspicion or evidence of connective tissue disease, cancer, higher serum aminotransferase concentrations
• Chronic cough; drug or alcohol abuse; pregnancy and breast feeding
• Unwillingness to sign informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

World Health Organization

OTHER

Sponsor Role: collaborator

Ministry of Health, Sri Lanka

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Selvarajah Mathu, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Ministry of Health

Shanthi Mendis, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

World Health Organization

Rezvi Sheriff, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colombo

Thilak Abeysekera, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Ministry of Health

Saroj Jayasinghe, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colombo

Locations

General (Teaching) Hospital, Anuradhapura

Anuradhapura, North Central Province, Sri Lanka

Countries

Sri Lanka

Central Contacts

Selvarajah Mathu, MBBS, MD

Role: CONTACT

mathuselvarajah@yahoo.com

94-77-7390628

Navaratnasingam Janakan, MBBS, MSc, MD

Role: CONTACT

navajanakan@yahoo.com

94-77-7489813

Facility Contacts

Selvarajah Mathu, MBBS, MD

Role: primary

mathuselvarajah@yahoo.com

94-77-7390628

Other Identifiers

NSF CKDu Research

Identifier Type: -

Identifier Source: org_study_id