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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Ministry of Health, Sri Lanka.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
World Health Organization
Information provided by (Responsible Party):
Ministry of Health, Sri Lanka
ClinicalTrials.gov Identifier:
NCT01624064
First received: June 16, 2012
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

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


Condition Intervention Phase
Renal Insufficiency, Chronic
Drug: Enalapril
Drug: Calcium Supplement
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind Clinical Trial to Examine the Renal Effects of an Angiotensin Converting Enzyme Inhibitor (Enalapril) in Adults With Chronic Kidney Disease of Uncertain Aetiology (CKDu)

Resource links provided by NLM:


Further study details as provided by Ministry of Health, Sri Lanka:

Primary Outcome Measures:
  • Proteinuria [ Time Frame: One year ] [ Designated as safety issue: No ]
    Numerous clinical trials have established that angiotensin-converting enzyme inhibitors (ACEI) are beneficial in slowing progression of renal 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 ACEI did show in glomerular disease and evidence is not so strong in tubulo-interstitial disease.

  • Estimated GFR [ Time Frame: One year ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • All cause mortality [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Cardiovascular mortality [ Time Frame: One year ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: August 2012
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Enalapril, Proteinuria < 1g/day Drug: Enalapril
2.5-20 mg/day
Other Name: Angiotensin Converting Enzyme Inhibitor
Placebo Comparator: Calcium, Proteinuria < 1g/day Drug: Calcium Supplement
Calcium 2.5-20 mg/day
Other Name: Calcium lactate
Active Comparator: Enalapril, Proteinuria > 1g/day Drug: Enalapril
2.5-20 mg/day
Other Name: Angiotensin Converting Enzyme Inhibitor
Placebo Comparator: Calcium, Proteinuria > 1g/day Drug: Calcium Supplement
Calcium 2.5-20 mg/day
Other Name: Calcium lactate

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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624064

Contacts
Contact: Selvarajah Mathu, MBBS, MD 94-77-7390628 mathuselvarajah@yahoo.com
Contact: Navaratnasingam Janakan, MBBS, MSc, MD 94-77-7489813 navajanakan@yahoo.com

Locations
Sri Lanka
General (Teaching) Hospital, Anuradhapura Not yet recruiting
Anuradhapura, North Central, Sri Lanka
Contact: Selvarajah Mathu, MBBS, MD    94-77-7390628    mathuselvarajah@yahoo.com   
Principal Investigator: Selvarajah Mathu, MBBS, MD         
Sponsors and Collaborators
Ministry of Health, Sri Lanka
World Health Organization
Investigators
Principal Investigator: Selvarajah Mathu, MBBS, MD Netherlands: Ministry of Health, Welfare and Sports
Principal Investigator: Shanthi Mendis, MBBS, MD World Health Organization
Principal Investigator: Rezvi Sheriff, MBBS, MD University of Colombo
Principal Investigator: Thilak Abeysekera, MBBS, MD Netherlands: Ministry of Health, Welfare and Sports
Principal Investigator: Saroj Jayasinghe, MBBS, MD University of Colombo
  More Information

No publications provided

Responsible Party: Ministry of Health, Sri Lanka
ClinicalTrials.gov Identifier: NCT01624064     History of Changes
Other Study ID Numbers: NSF CKDu Research
Study First Received: June 16, 2012
Last Updated: June 19, 2012
Health Authority: Sri Lanka: Ministry of Healthcare & Nutrition

Keywords provided by Ministry of Health, Sri Lanka:
Renal Insufficiency, Chronic
Uncertain aetiology
ACEI

Additional relevant MeSH terms:
Renal Insufficiency, Chronic
Kidney Diseases
Renal Insufficiency
Kidney Failure, Chronic
Urologic Diseases
Angiotensin-Converting Enzyme Inhibitors
Enalapril
Enalaprilat
Calcium, Dietary
Enzyme Inhibitors
Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Bone Density Conservation Agents
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014