Study of High Dosage of Losartan in Comparison to Low Dose of Losartan in Heart Failure Patients

NCT02238457 | Withdrawn Phase 4

• 1 other identifier: Project 103-10
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The sympathetic nervous system, a part of the nervous system that stimulates the heart via release of substances, noradrenaline and adrenaline (combined called catecholamines), becomes activated in people with heart failure. As these people become sicker, the nervous system becomes more active, causing further damage to the heart. Large trials have shown that Angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with heart failure. Higher doses of these drugs are more effective than lower doses. Studies show that ACE-inhibitors decrease catecholamine levels. This could be why congestive heart failure (CHF) patients taking this class of drugs show improvement in heart function. There are several ways of measuring the activity of the sympathetic nervous system. The most common measurement is to test the blood for catecholamine levels. This is not very reliable or reproducible. Microneurography is a new technique used to measure sympathetic nerve activity. A small electrode (comparable to an acupuncture needle) is placed in a muscle nerve and hooked up to a stimulator and a recorder. It produces direct recordings of skeletal muscle nerve traffic. Both the rate and amplitude of the burst can be measured. The results in this technique are highly reproducible. By using this technique we get a more accurate picture of how the nervous system responds to medications given to treat heart failure. Losartan (Cozaar) is an angiotensin II type 1 (AT1) receptor blocker. It blocks the binding of angiotensin II, a hormone that constricts blood vessels. As a result the blood vessels remain relaxed, leading to a reduction in the workload of the heart. Minor decreases in blood catecholamine levels have been reported with a low dose of this drug. The purpose of this study is to see whether a high dose of losartan (200 mg) has a greater effect on the sympathetic nervous system than a low dose of losartan (50 mg) does. A total of 30 participants will be recruited. Participants will be assigned to one of two groups: high-dose, in which subjects will receive treatment of 200 mg/day of losartan, and low-dose, in which subjects will receive treatment of 50 mg/day of losartan. Via microneurography the investigators will measure the difference in sympathetic activity in subjects in high-dose vs low-dose losartan. The investigators expect to see further decrease in sympathetic activity in high-dose group than in low-dose group.

Conditions

Heart Failure

Keywords

Heart failure; Losartan

Outcome Measures

Primary Outcomes (1)

• Effect of losartan on the sympathetic nervous system.

  Assessed by microneurographic recordings of muscle sympathetic nerve activity from the peroneal nerve.

  10 weeks

Secondary Outcomes (2)

• Change in plasma catecholamines.

  10 weeks

• Change in central hemodynamics.

  10 weeks

Study Arms (2)

Low dose losartan

ACTIVE COMPARATOR

Low dose losartan

Drug: Low dose losartan

High dose losartan

ACTIVE COMPARATOR

High dose losartan

Drug: High dose losartan

Interventions

Low dose losartan DRUG

25 mg losartan bid for 10 weeks

Also known as: losartan (Cozaar)

Low dose losartan

High dose losartan DRUG

50 mg, 75 mg, or 100 mg bid for 10 weeks. Dose will be determined by the medical doctor depending on patients' tolerability

Also known as: Losartan (Cozaar)

High dose losartan

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females age between 21 and 75 years
• Diagnosis of mild to moderate congestive heart failure
• Coronary angiography identifying coronary artery disease as the likely cause of congestive heart failure
• Left Ventricular (LV) ejection fraction between 20 to 40 percent on echocardiography or RNA
• Sinus rhythm

You may not qualify if:

• Insulin-dependent diabetes mellitus
• Hypertension (higher than 140/90 mmHg at rest)
• Use of sympatholytic agents such as clonidine, methyldopa, reserpine
• Significant non-cardiac disease, possibly affecting cardiovascular regulation
• Autonomic neuropathy of any cause
• Leg injuries with nerve damage
• Poor bladder control
• Recent history of alcoholism, drug abuse, significant psychiatric disorders
• Known adverse events to AT1-receptor blockers
• Unlikely to tolerate being off digoxin and off blockers of the RAS for a short period
• Ischemic event within past 3 months
• Serum creatinine higher than 200 mmol/L
• Patients taking digoxin for atrial fibrillation
• Patients who require treatment with aldactone
• Patients with more than mild stable angina while on beta-blockers and/or calcium antagonists

Sponsors & Collaborators

• Baker Heart and Diabetes Institute: lead

MeSH Terms

Conditions

Heart Failure

Interventions

Losartan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Markus P Schlaich

  Baker IDI Heart & Diabetes Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: A/Prof

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: September 12, 2014
• Last Updated: November 2, 2018

Record last verified: 2018-11