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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by Nanfang Hospital of Southern Medical University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier:
NCT00630708
First received: February 28, 2008
Last updated: February 16, 2011
Last verified: February 2011
History of Changes
  Purpose

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.


Condition Intervention
Renal Insufficiency, Chronic
 Drug: Benazepril
Drug: Losartan
Drug: Benazepril+Losartan

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety of Dual Blockage of Rennin-angiotensin System in Patients With Advanced Renal Insufficiency

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Nanfang Hospital of Southern Medical University:

Primary Outcome Measures:
  • The proportion of patients with increase in serum potassium ≥6.0 mmol/L. [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The proportion of patients with serum creatinine increase >30% [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
  • The proportion of patients with drug-related cough [ Time Frame: Every 4 weeks ] [ Designated as 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 ] [ Designated as safety issue: Yes ]
  • The proportion of patients with non-fatal cardiovascular events [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 309
Study Start Date: February 2008
Estimated Study Completion Date: May 2012
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Benazepril group
 Drug: Benazepril
20 mg per day
Other Name: Lotensin
Active Comparator: 2
Losartan group
 Drug: Losartan
100 mg per day
Other Name: Cozaar
Active Comparator: 3
Benazepril+Losartan group
 Drug: Benazepril+Losartan
combination treatment of 10 mg benazepril and 50 mg losartan per day
Other Name: Lotensin+Cozaar

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00630708

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

Locations
China, Guangdong
Renal Division, Nanfang Hospital,Southern Medical University Recruiting
Guangzhou, Guangdong, China, 510515
Contact: Fan Fan Hou, M.D., Ph.D.     86-20-61641597     ffhou@public.guangzhou.gd.cn    
Principal Investigator: Fan Fan Hou, M.D., Ph.D.            
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University
Investigators
Principal Investigator: Fan Fan Hou, M.D.,Ph.D. Renal Division, Nanfang Hospital,Southern Medical University
  More Information

No publications provided

Responsible Party: Fan Fan Hou, Renal Division, Nanfang Hospital, Southern Medical University
ClinicalTrials.gov Identifier: NCT00630708     History of Changes
Other Study ID Numbers: Nanfang200803
Study First Received: February 28, 2008
Last Updated: February 16, 2011
Health Authority: China: Food and Drug Administration

Keywords provided by Nanfang Hospital of Southern Medical University:
Renal insufficiency
Benazepril
Losartan
combination treatment
Safety

Additional relevant MeSH terms:
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Benazepril
Losartan
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on May 21, 2013