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

Sponsor:	Nanfang Hospital
Information provided by:	Nanfang Hospital
ClinicalTrials.gov Identifier:	NCT00630708

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:

MedlinePlus related topics: Potassium

Drug Information available for: Benazepril hydrochloride Benazepril Losartan Losartan potassium Lotrel

U.S. FDA Resources

Further study details as provided by Nanfang Hospital:

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:

Serum creatinine concentration of 3.0 to 5.0 mg per deciliter (265 to 442 µmol/L)
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
non-diabetic renal disease
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])
had not received ACE inhibitors or ARBs for at least two weeks before screening

Exclusion Criteria:

No history of allergic reaction to drugs, especially ACE inhibitors and/or ARBs
Hyper-or hypokalemia (serum potassium concentration 5.6 mmol per liter or more，or 3.5 mmol per liter or less)
Malignant hypertension (blood pressure >180/120 mm Hg) or blood pressure <110mm Hg without antihypertensive treatment
Treatment with drugs affecting serum potassium such as diuretic, β2 receptor blocker et al.
Treatment with corticosteroids, non-steroidal anti-inflammatory drugs, or immunosuppressive drugs, especially ciclosporin A
Myocardial infarction or cerebrovascular accident in the year preceding the trial
Nephrotic syndrome (albuminaemia less than 25 g/L)
Renovascular disease or connective-tissue disease
Obstructive uropathy
Immediate need for dialysis
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

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: State Food and Drug Administration

Keywords provided by Nanfang Hospital:

Renal insufficiency
Benazepril
Losartan
combination treatment
Safety

Additional relevant MeSH terms:

Renal Insufficiency, Chronic
Renal Insufficiency
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 February 09, 2012