Safety of Dual Blockage of Rennin-angiotensin System in Patients With Advanced Renal Insufficiency (SDBRAS)

The primary aim of the present study is to assess the safety of combined treatment of benazepril (an ACE inhibitor) or losartan (an ARB) in non-diabetic patients with advanced renal insufficiency.

Study Overview

• Status: Terminated
• Conditions: Renal Insufficiency, Chronic
• Intervention / Treatment: Drug: Benazepril; Drug: Losartan; Drug: Benazepril+Losartan

Detailed Description

Interruption of the renin-angiotensin systerm (RAS) with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) slows the progression of chronic renal insufficiency in the presence or absence of diabetes. Even for advanced chronic renal insufficiency (stage 4 CKD), ACE inhibitors and ARBs can still provide renoprotection. Some clinical studies showed that dual RAS blockage seemed to enhance the antiproteinuric effect compared with single-agent ACE inhibitor or ARB and then improve renal survival. However, in the only one randomized controlled trial investigating the renoprotection of combined ACE inhibitor and ARB for mild or moderate chronic renal insufficiency (the mean creatinine value is 2.9mg/dl), the incidence of hyperkalemia was increased in combination therapy compared with monotherapy. Although increase of hyperkalemia was not statistical significant, it suggested that combination treatment of ACEI and ARB might increase the incidence of hyperkalemia in patients with advanced renal insufficiency. However, it is still undetermined whether combination treatment of ACE inhibitor and ARB is safe as an ACE inhibitor or ARB monotherapy in advanced non-diabetic chronic renal insufficiency (stage 4 CKD). The primary aim of the present study is to assess the safety of combined treatment of benazepril (an ACE inhibitor) or losartan (an ARB) in non-diabetic patients with advanced renal insufficiency.

• Study Type: Interventional
• Enrollment (Anticipated): 309
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Renal Division, Nanfang Hospital,Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Serum creatinine concentration of 3.0 to 5.0 mg per deciliter (265 to 442 µmol/L)
2. Creatinine clearance of 15 to 30 ml per minute per 1.73m2, with variations of less than 30 percent in the three months before screening evaluation
3. non-diabetic renal disease
4. Persistent heavier proteinuria (defined by urinary protein excretion of more than 0.3g per day for three or more months without evidence of urinary tract infection or overt heart failure [a New York Heart Association class of Ⅲ or Ⅳ])
5. had not received ACE inhibitors or ARBs for at least two weeks before screening

Exclusion Criteria:

1. No history of allergic reaction to drugs, especially ACE inhibitors and/or ARBs
2. Hyper-or hypokalemia (serum potassium concentration 5.6 mmol per liter or more，or 3.5 mmol per liter or less)
3. Malignant hypertension (blood pressure >180/120 mm Hg) or blood pressure <110mm Hg without antihypertensive treatment
4. Treatment with drugs affecting serum potassium such as diuretic, β2 receptor blocker et al.
5. Treatment with corticosteroids, non-steroidal anti-inflammatory drugs, or immunosuppressive drugs, especially ciclosporin A
6. Myocardial infarction or cerebrovascular accident in the year preceding the trial
7. Nephrotic syndrome (albuminaemia less than 25 g/L)
8. Renovascular disease or connective-tissue disease
9. Obstructive uropathy
10. Immediate need for dialysis
11. Pregnancy or breastfeeding

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Benazepril group	Drug: Benazepril; 20 mg per day; Other Names: Lotensin
Active Comparator: 2; Losartan group	Drug: Losartan; 100 mg per day; Other Names: Cozaar
Active Comparator: 3; Benazepril+Losartan group	Drug: Benazepril+Losartan; combination treatment of 10 mg benazepril and 50 mg losartan per day; Other Names: Lotensin+Cozaar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients with increase in serum potassium ≥6.0 mmol/L.	Every 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients with serum creatinine increase >30%	Every 4 weeks
The proportion of patients with drug-related cough	Every 4 weeks
The proportion of patients with hopotension (systolic blood pressure <110 mmHg despite withdrawal of all additional antihypertensive medication)	Every 4 weeks
The proportion of patients with non-fatal cardiovascular events	Every 4 weeks

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Investigators: Principal Investigator: Fan Fan Hou, M.D.,Ph.D., Renal Division, Nanfang Hospital,Southern Medical University

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: February 28, 2008
• First Submitted That Met QC Criteria: March 6, 2008
• First Posted (Estimate): March 7, 2008

Study Record Updates

• Last Update Posted (Estimate): April 5, 2016
• Last Update Submitted That Met QC Criteria: April 2, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Safety; Benazepril; Losartan; Renal insufficiency; combination treatment
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Losartan; Benazepril
• Other Study ID Numbers: Nanfang200803