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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Horng Chen, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01678794
First received: August 31, 2012
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
"Cardiorenal Syndrome (CRS)"
Drug: Candesartan
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change in Glomerular Filtration Rate (mL/min/1.73 m2) [ Time Frame: baseline to 3 months ] [ Designated as safety issue: No ]
  • change in urinary Sodium excretion [ Time Frame: baseline to 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 76
Study Start Date: February 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Candesartan Drug: 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
Other Name: Atacand
Placebo Comparator: Placebo 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Subjects who are already taking AT1 receptor blocker will be excluded. Aldosterone antagonist, antiarrhythmic medications and other vasodilators will be allowed; however, all medications must be at stable doses 4 weeks prior to enrollment. Subjects taking nonsteroidal anti-inflammatory drugs (NSAIDs) except aspirin will not be able to increase their medication dose for the duration of the study. Subjects will be excluded if they have had a prior diagnosis of intrinsic renal disease, including renal artery stenosis of > 50%, or if they meet any one of the exclusion criteria listed below.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01678794

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Lynn Harstad    507-284-4838    harstad.lynn@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
  More Information

No publications provided

Responsible Party: Horng Chen, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01678794     History of Changes
Other Study ID Numbers: 09-003284, 1R01HL084155-01A2
Study First Received: August 31, 2012
Last Updated: May 30, 2014
Health Authority: United States: Data and Safety Monitoring Board

Keywords provided by Mayo Clinic:
Chronic heart failure (CHF)
cardiac and renal dysfunction

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardio-Renal Syndrome
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Cardiovascular Diseases
Candesartan
Candesartan cilexetil
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014