Official Title: “Safety of Dual Blockage of Rennin-Angiotensin System in Patients With Advanced Renal Insufficiency”

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

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety Study

Study Primary Completion Date: February 2010

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.

Intervention(s) in this Clinical Trial

• Drug: Benazepril
  • 20 mg per day
• Drug: Losartan
  • 100 mg per day
• Drug: Benazepril+Losartan
  • combination treatment of 10 mg benazepril and 50 mg losartan per day

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Benazepril group
• Active Comparator: 2
  • Losartan group
• Active Comparator: 3
  • Benazepril+Losartan group

Primary Measures

• The proportion of patients with increase in serum potassium ≥6.0 mmol/L.
  • Time Frame: Every 4 weeks
    Safety Issue?: Yes

Secondary Measures

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

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Nanfang Hospital

Overall Clinical Trial Officials and Contacts

Fan Fan Hou, M.D.,Ph.D. Principal Investigator Renal Division, Nanfang Hospital,Southern Medical University  

Overall Contact: Fan Fan Hou, M.D., Ph.D. 86-20-61641597 ffhou@public.guangzhou.gd.cn

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00630708

Study ID Number: Nanfang200803

ClinicalTrials.gov Identifier: NCT00630708

Health Authority: China: State Food and Drug Administration