CR Aim #2 - AT1 Receptor Blockade & ACE Inhibition Effect on Humoral Function

NCT ID: NCT01678794

Last Updated: 2021-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2016-06-29

Brief Summary

To advance our understanding of the mechanisms of human cardiorenal syndrome with emphasis upon the interaction of diuretic therapy and the renal-angiotensin-aldosterone -system and cGMP pathway.

The belief is that the chronic AT1 receptor blockade in subjects with compensated CHF and renal dysfunction will improve renal function with increased sodium excretion, glomerular filtration rate and effective renal plasma flow and renal function reserve as compared to the response of placebo-treated subjects.

Detailed Description

IRB # 09-003284, "Specific Aims 2: Define in humans with compensated CHF and renal dysfunction, the modulating action of chronic AT1 receptor blockade in addition to ACE inhibition on cardiorenal and humoral function", involving 12 weeks of study drug (Candesartan or placebo) starting at 4 mg daily and doubling every 2 weeks to 16 mg, if tolerated. Safety labs are performed one week after each dose increase (end of weeks 1, 3 and 5), and in week 10 of the study. Participants are monitoring their blood pressure weekly, and are aware to watch for symptoms of hypotension (lightheadedness, dizziness, blurred vision). Renal clearance testing and ECHO are performed at the start and end of the 12 weeks of study medication in the 5-Domitilla Clinical Research Unit.

Conditions

Cardiorenal Syndrome (CRS)

Keywords

Chronic heart failure (CHF); cardiac and renal dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Candesartan

Group Type: EXPERIMENTAL

Candesartan

Intervention Type: DRUG

4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated

Interventions

Candesartan

4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated

Intervention Type: DRUG

Placebo

4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated

Intervention Type: DRUG

Other Intervention Names

Atacand

Eligibility Criteria

Inclusion Criteria

• Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 48 months.
• Stable New York Heart Association (NYHA) class II and III symptoms as defined by: no change in NYHA symptoms over the past 3 months, on stable doses of ACE inhibitor, beta blocker, digoxin and furosemide over the last 4 weeks and no episode of decompensated CHF over the past 6 months.
• Calculated creatinine clearance of equal or less than 80 ml/min and greater than 20 ml/min, using the MDRD formula assessed within the past 48 months and a confirmatory calculated creatinine clearance equal or less than 80 ml/min and greater than 20 ml/min at the time of enrollment.

Exclusion Criteria

• Prior diagnosis of intrinsic renal diseases including renal artery stenosis of > 50%
• Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
• Hospitalization for decompensated CHF during the past 6 months
• Subjects that are taking AT1 receptor blockers
• Myocardial infarction within 6 months of screening
• Unstable angina within 6 months of screening, or any evidence of myocardial ischemia
• Significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
• Severe congenital heart diseases
• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
• Second or third degree heart block without a permanent cardiac pacemaker
• Stroke within 3 months of screening, or other evidence of significantly compromised CNS perfusion
• ALT >1.5 times the upper limit of normal
• Serum sodium of < 125 mEq/dL or > 160 mEq/dL
• Serum potassium of < 3.5 mEq/dL or > 5.7 mEq/dL
• Serum digoxin level of > 2.0 ng/ml
• Hemoglobin < 9 gm/dl
• Other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data
• Received an investigational drug within 1 month prior to dosing
• Patients with an allergy to iodine.
• Female subject who is pregnant or breastfeeding
• In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Horng Chen

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Horng H. Chen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Foundation

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

1R01HL084155-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

09-003284

Identifier Type: -

Identifier Source: org_study_id