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

NCT ID: NCT00630708

Last Updated: 2016-04-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 309 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2014-03-31

Brief Summary

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.

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.

Conditions

Renal Insufficiency, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Benazepril group

Group Type: ACTIVE_COMPARATOR

Benazepril

Intervention Type: DRUG

20 mg per day

2

Losartan group

Group Type: ACTIVE_COMPARATOR

Losartan

Intervention Type: DRUG

100 mg per day

3

Benazepril+Losartan group

Group Type: ACTIVE_COMPARATOR

Benazepril+Losartan

Intervention Type: DRUG

combination treatment of 10 mg benazepril and 50 mg losartan per day

Interventions

Benazepril

20 mg per day

Intervention Type: DRUG

Losartan

100 mg per day

Intervention Type: DRUG

Benazepril+Losartan

combination treatment of 10 mg benazepril and 50 mg losartan per day

Intervention Type: DRUG

Other Intervention Names

Lotensin; Cozaar; Lotensin+Cozaar

Eligibility Criteria

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

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

Sponsors

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fan Fan Hou, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Renal Division, Nanfang Hospital,Southern Medical University

Locations

Renal Division, Nanfang Hospital,Southern Medical University

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

Nanfang200803

Identifier Type: -

Identifier Source: org_study_id