Renal Protective Effects of Renin Angiotensin System (RAS) Inhibitor in Peritoneal Dialysis Patients

Effects of Benazepril,Valsartan or Combination of Both on Residual Renal Function in Peritoneal Dialysis Patients

This is a multicentre study examining the effectiveness of angiotension converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) or a combination of both in reducing the rate of decline in residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD) patients.

Study Overview

• Status: Completed
• Conditions: Renal Function Disorder
• Intervention / Treatment: Drug: Benazepril; Drug: Valsartan; Drug: Benazepril+Valsartan; Drug: Control

Detailed Description

RRF has been shown to decline progressively with time on dialysis in both CAPD and hemodialysis. Although RRF is an important determinant of mortality and morbidity in peritoneal dialysis (PD) patients, few studies have addressed therapeutic approaches for preserving RRF after the initiation of dialysis therapy. Blockade of the renin-angiotensin system by ACEI or ARB is a well-established approach for renoprotection in pre-dialysis chronic kidney disease patients. Up to now, only two trials showed that an ACEI, ramipril, and ARB, valsartan , were effective in the preservation of RRF of CAPD patients. However it is important to point out that the evidence cited has limitations. First, the trial only involved patients from one university teaching hospital. Second, transport characteristics, were not assessed before the start of the study. Third, the trial was too small to detect potentially important differences in health care use and survival between groups. Therefore, whether both ACEI and ARB preserve RRF, improve clinical outcomes and decrease health care use and costs should be tested in much longer and larger studies involving multiple sites. In order to confirm these findings, here the investigators will perform prospective, randomized, open-label and multiple center study to address long-term effects of ACEI, ARB and combination of both therapy on RRF in Patients on CAPD.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • GuangZhou, Guangdong, China, 510080
      • The 1st Affiliated Hospital, Sun Yet-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients received CAPD more than 1 months
• Subjects of either sex, 20-75 years old
• Residual GFR of 3mL/min per 1.73 m2 or more
• With hypertension
• No history of taking an ACE inhibitor or angiotensin-receptor blockers for at least 1 month
• Provision of written informed consent by subject or guardian

Exclusion Criteria:

• Underlying medical conditions, such as congestive heart failure, or therapy with an ACE inhibitor or ARB
• Peritonitis or volume overload within the preceding 1 month
• Myocardial infarction within the preceding 6 months
• Clinically significant valvular disease
• Malignant hypertension
• History of hypertensive encephalopathy or cerebrovascular accident within the preceding 6 months
• Any condition that may have precluded a patient from remaining in the study, such as alcohol or drug abuse, chronic liver disease, malignant disease, or psychiatric disorder
• History of allergy or intolerance to an ACE inhibitor or ARB
• Participation in another clinic trial within 2 weeks prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACE inhibitor, benazepril; Benazepril will be started at 10 mg/day and will be up-titrated to 20 mg/day according to BP control and tolerability.	Drug: Benazepril; Patients with hypertension will take 10-20mg benazepril per day, antihypertensive agents other than ACE inhibitors and ARBs will be allowed. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 120-140/70-90 mmHg.; Other Names: Benazepril group
Experimental: Angiotensin receptor blocker, valsartan; Valsartan will be started at 80 mg/day and will be up-titrated to 160 mg/day according to BP control and tolerability.	Drug: Valsartan; Patients with hypertension will take 80-160mg valsartan per day, antihypertensive agents other than ACE inhibitors and ARBs will be allowed. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 120-140/70-90 mmHg.; Other Names: Valsartan group
Experimental: RAS inhibitors, benazepril+valsartan; Benazepril will be started at 10 mg/day and will be up-titrated to 20 mg/day, and valsartan will be started at 80 mg/day and will be up-titrated to 160 mg/day according to BP control and tolerability.	Drug: Benazepril+Valsartan; Patients with hypertension will take 10-20mg benazepril plus 80-160mg valsartan per day, antihypertensive agents other than ACE inhibitors and ARBs will be allowed. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 120-140/70-90 mmHg.; Other Names: Benazepril plus Valsartan group
Active Comparator: non-RAS inhibitors, control; Drug: antihypertensive agents, except ACE inhibitors and ARBs. Administration of antihypertensive agents will select as follows: CCB→β-blocker→α-blocker.	Drug: Control; Patients in the control group will administer antihypertensive agents, except ACE inhibitors and ARBs. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 120-140/70-90 mmHg.; Other Names: Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The longitudinal change in residual glomerular filtration rate (GFR)	Residual GFR is defined as the average of 24-hour urinary urea and creatinine clearances.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dialysis adequacy	Indices of the adequacy of dialysis include Kt/V and weekly creatinine clearance assessed by 24-hour dialysate and urinary collection.	3 years
Peritoneal membrane function	Peritoneal membrane function assessed by standard peritoneal equilibration test.	3 years
Blood pressure	Office systolic and diastolic blood pressure measurement during follow up period.	3 years
The time to anuria	Anuria is defined as urine volume < 100ml/d.	3 years
Number of participants not alive	Death from any cause.	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Jianbo Liang, M.D., 2nd Affiliated Hospital, Guangzhou Medical College; Principal Investigator: Yunhua Liao, M.D., 1st Affiliated Hospital, Guangxi Medical University; Principal Investigator: Xinzhou Zhang, M.D. & Ph.D., Shenzhen People's Hospital; Principal Investigator: Fei Xiong, M.D., Wuhan No.1 hospital; Principal Investigator: Hao Zhang, M.D., 3rd Xiangya Hospital, Central South University; Principal Investigator: Ping Fu, M.D. & Ph.D., West China Hospital; Principal Investigator: Yonggui Wu, M.D.& Ph.D., 1st Affiliated Hospital, Anhui Medical University; Principal Investigator: Minghui Zhao, M.D.&Ph.D., Peking University First Hospital; Principal Investigator: Xuewang Li, M.D., Peking Union Medical College Hospital; Principal Investigator: Li Hao, MD, 2nd Affiliated Hospital, Anhui Medical University

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: July 22, 2008
• First Submitted That Met QC Criteria: July 22, 2008
• First Posted (Estimate): July 24, 2008

Study Record Updates

• Last Update Posted (Estimate): May 20, 2015
• Last Update Submitted That Met QC Criteria: May 18, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Continuous Ambulatory Peritoneal Dialysis; Residual Renal Function; Angiotensin-converting Enzyme Inhibitor; Angiotensin II Receptor Blocker; Renin angiotensin system inhibitor
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Valsartan; Benazepril
• Other Study ID Numbers: PDRRF