Heart FailurePhase 4NCT02238457
Study of High Dosage of Losartan in Comparison to Low Dose of Losartan in Heart Failure Patients
A Phase 4 study testing Low dose losartan and High dose losartan in people with Heart Failure, run by Baker Heart and Diabetes Institute.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Low dose losartan and High dose losartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Start not givento not given
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
- Patients on coumadin
About this study
Official title: Effects of Low-Dose vs High-dose Losartan on Sympathetic Hyperactivity in Patients With Congestive Heart Failure
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.
Read more
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
- Being tested
- Low dose losartan, High dose losartan
- Keywords
- Heart failure, Losartan
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low dose losartanDrug
Also called losartan (Cozaar)
25 mg losartan bid for 10 weeks
High dose losartanDrug
Also called Losartan (Cozaar)
50 mg, 75 mg, or 100 mg bid for 10 weeks. Dose will be determined by the medical doctor depending on patients' tolerability
| Study group | Role | What they receive |
|---|---|---|
| Low dose losartan | Active comparator | Low dose losartan Receives: Drug: Low dose losartan |
| High dose losartan | Active comparator | High dose losartan Receives: Drug: High dose losartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of losartan on the sympathetic nervous system.
Assessed by microneurographic recordings of muscle sympathetic nerve activity from the peroneal nerve.
Measured: 10 weeks
Secondary outcomes (2)
Change in plasma catecholamines.
Plasma catecholamines will be measured by High-performance liquid chromatography (HPLC). Samples will be collected for plasma aldosterone, plasma renin and plasma angiotensin II.
Measured: 10 weeks
Change in central hemodynamics.
Invasive measurement of central hemodynamic parameters; heart rate, blood pressure, cardiac output (CO), pulmonary capillary wedge pressure (PCWP), right arterial pressure (RAP).
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2014 (estimated)
Why it stopped: Difficulty recruiting patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baker Heart and Diabetes Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Markus Schlaich, Baker Heart and Diabetes Institute
- Investigators
- Markus P Schlaich, Principal investigator, Baker IDI Heart & Diabetes Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02238457
- Sponsor's protocol ID
- Project 103-10
- Status last verified
- Nov 2018
- First submitted
- 4 Jun 2012
- Last updated
- 2 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Low-Dose vs High-dose Losartan on Sympathetic Hyperactivity in Patients With Congestive Heart Failure
- ClinicalTrials.gov ID
- NCT02238457
- Acronym / sponsor ID
- Project 103-10
- Conditions
- Heart Failure
- Keywords
- Heart failure, Losartan
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Difficulty recruiting patients
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Baker Heart and Diabetes InstituteUniversity, hospital or other
- First posted
- 12 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low dose losartan | Active comparator | Drug: Low dose losartanLow dose losartan |
| High dose losartan | Active comparator | Drug: High dose losartanHigh dose losartan |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low dose losartanAlso: losartan (Cozaar)25 mg losartan bid for 10 weeks | Drug | Low dose losartan |
| High dose losartanAlso: Losartan (Cozaar)50 mg, 75 mg, or 100 mg bid for 10 weeks. Dose will be determined by the medical doctor depending on patients' tolerability | Drug | High dose losartan |
Primary outcome
Effect of losartan on the sympathetic nervous system.
Time frame: 10 weeks
Assessed by microneurographic recordings of muscle sympathetic nerve activity from the peroneal nerve.
2 secondary outcomes
Change in plasma catecholamines.
Time frame: 10 weeks
Change in central hemodynamics.
Time frame: 10 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus P Schlaich principal investigator
Baker IDI Heart & Diabetes Institute
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Low dose losartan and High dose losartan in people with Heart Failure, run by Baker Heart and Diabetes Institute.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of losartan on the sympathetic nervous system. (time frame: 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2018.