Clinical trial NCT00630708: Safety of Dual Blockage of Rennin-angiotensin System in Patients With Advanced Renal Insufficiency
Official title: Safety of Dual Blockage of Rennin-angiotensin System in Patients With Advanced Renal Insufficiency
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Renal Insufficiency, Chronic
Keywords: Renal insufficiency
Benazepril
Losartan
combination treatment
Safety
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2008-03-07
Enrollment: 309
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The proportion of patients with increase in serum potassium ≥6.0 mmol/L.
timeFrame: Every 4 weeks
Secondary outcomes:
measure: The proportion of patients with serum creatinine increase >30%
timeFrame: Every 4 weeks
measure: The proportion of patients with drug-related cough
timeFrame: Every 4 weeks
measure: The proportion of patients with hopotension (systolic blood pressure <110 mmHg despite withdrawal of all additional antihypertensive medication)
timeFrame: Every 4 weeks
measure: The proportion of patients with non-fatal cardiovascular events
timeFrame: Every 4 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Renal Division, Nanfang Hospital,Southern Medical University
state: Guangdong
Study officials:
affiliation: Renal Division, Nanfang Hospital,Southern Medical University
name: Fan Fan Hou, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: