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

Renal Insufficiency, Chronic Clinical Trial

— SDBRAS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00630708
• Other study ID #: Nanfang200803
• Status: Terminated
• Phase: N/A
• First received: February 28, 2008
• Last updated: April 2, 2016
• Start date: February 2008
• Est. completion date: March 2014

Study information

• Verified date: April 2016
• Source: Nanfang Hospital of Southern Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 309
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 ? or ?])

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, ß2 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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

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

Locations

Country	Name	City	State
China	Renal Division, Nanfang Hospital,Southern Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of patients with increase in serum potassium =6.0 mmol/L.		Every 4 weeks	Yes
Secondary	The proportion of patients with serum creatinine increase >30%		Every 4 weeks	Yes
Secondary	The proportion of patients with drug-related cough		Every 4 weeks	Yes
Secondary	The proportion of patients with hopotension (systolic blood pressure <110 mmHg despite withdrawal of all additional antihypertensive medication)		Every 4 weeks	Yes
Secondary	The proportion of patients with non-fatal cardiovascular events		Every 4 weeks	Yes