Tovinontrine for Heart Failure
(Cycle-1-REF Trial)
Recruiting at 121 trial locations
EM
GB
Overseen ByGail Berman
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Cardurion Pharmaceuticals, Inc.
Must be taking: Guideline-directed HF therapy
Prior Safety DataThis treatment has passed at least one previous human trial
Trial Summary
What is the purpose of this trial?
The purpose of this study is to evaluate the safety and effectiveness of tovinontrine compared to placebo to lower NT-proBNP in patients with chronic heart failure with reduced ejection fraction.
Will I have to stop taking my current medications?
The trial requires that you stay on your current heart failure medications at stable doses for at least 4 weeks before and during the screening period, with no planned changes after joining the study.
What data supports the effectiveness of the drug Tovinontrine for heart failure?
Research Team
GB
Gail Berman
Principal Investigator
Senior VP Head, Clinical Development Cardurion
Eligibility Criteria
This trial is for adults with chronic heart failure who have a reduced ability of the heart to pump blood (ejection fraction ≤ 40%). Participants must show certain levels of NT-proBNP, a marker indicating heart stress, and have symptoms or signs of heart failure. They should be on stable heart failure medication for at least 4 weeks with no recent changes.Inclusion Criteria
Has evidence in the medical history supporting a diagnosis of clinical HF syndrome, NYHA functional class II to III, with the duration of at least 6 months prior to the time of Screening. The HF syndrome is defined by documentation of 1 or more of the following: At least 1 of the typical symptoms due to HF such as dyspnea and/or fatigue limiting exercise capacity; At least 1 of the typical signs of HF such as peripheral edema, elevated jugular venous pressure, pulmonary crackles; or Hospitalization, emergency department visit, or outpatient visit for HF requiring intravenous (IV) or subcutaneous (SQ) diuresis within the past 12 months; Has ejection fraction (EF) ≤ 40% by transthoracic echocardiogram (TTE) performed and interpreted locally at the time of Screening; Has NT-proBNP level ≥ 600 pg/mL at the time of Screening. Patients with atrial fibrillation or flutter at the time of Screening are required to have an NT-proBNP level of ≥ 1000 pg/mL at the time of Screening; Is on stable optimized doses of guideline-directed HF therapy, per Investigator's clinical judgement, for a minimum of 4 weeks prior to the time of Screening and during Screening, with no planned changes after randomization; Has had no addition of new guideline-directed HF therapy within the 3 months prior to the time of Screening or during the Screening Period;
Exclusion Criteria
Has a documented EF >40% by TTE within 6 months of the time of Screening or during the Screening Period; Has evidence of recent HF exacerbation defined by hospitalization or requirement for IV or SQ diuretics within 60 days of the time of Screening or during the Screening Period; Has a requirement for routine, scheduled outpatient IV infusions for HF (ie, inotropes, vasodilators, or diuretics) or routinely scheduled ultrafiltration; Has elective interventions (eg, percutaneous coronary intervention, device implantations, percutaneous structural heart disease interventions, cardiac and non-cardiac surgery) planned to occur during involvement in this study; Has acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, or carotid angioplasty within 60 days of the time of Screening or during the Screening Period; Has had a prior or planned orthotopic heart transplantation; Has presence of or plan for mechanical circulatory support;
Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive tovinontrine or placebo to evaluate safety and effectiveness in lowering NT-proBNP
12 weeks
Regular visits for assessments and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Tovinontrine
Trial Overview The study tests Tovinontrine's effectiveness in lowering NT-proBNP levels compared to a placebo in patients with chronic heart failure. The goal is to see if Tovinontrine can improve symptoms by helping the failing heart work better.
Participant Groups
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Tovinontrine (CRD-750) - medium doseExperimental Treatment1 Intervention
Group II: Tovinontrine (CRD-750) - low doseExperimental Treatment1 Intervention
Group III: Tovinontrine (CRD-750) - high doseExperimental Treatment1 Intervention
Group IV: PlaceboPlacebo Group1 Intervention
Find a Clinic Near You
Who Is Running the Clinical Trial?
Cardurion Pharmaceuticals, Inc.
Lead Sponsor
Trials
6
Recruited
740+
Findings from Research
Tolvaptan, a vasopressin receptor 2 antagonist, effectively improved congestive symptoms in heart failure patients with volume overload within 14 days, regardless of treatment duration (14DS vs. 15DL).
Patients in the longer treatment group (15DL) showed statistically significant further improvements in symptoms like lower limb edema and dyspnea after 2 weeks, although many patients may not have responded well, indicating a need for better identification of effective responders.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Who Needs Longer Tolvaptan Treatment?Kinugawa, K., Inomata, T., Sato, N., et al.[2018]
In the SMILE study, tolvaptan was found to be equally effective in treating congestive heart failure symptoms in patients aged 80 and older compared to those younger than 80, indicating its efficacy across age groups.
The safety profile of tolvaptan was favorable in older patients, with a lower incidence of thirst compared to younger patients, but a recommendation was made to start at lower doses in older patients to avoid the risk of hypernatremia.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Effectiveness and adverse events of tolvaptan in octogenarians with heart failure. Interim analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study).Kinugawa, K., Inomata, T., Sato, N., et al.[2018]
Childhood cancer survivors, particularly those treated with anthracyclines, face a significantly increased risk of cardiac dysfunction and heart failure, with a 15-fold higher likelihood of developing late treatment-related heart failure compared to the general population.
Cardio-oncology is emerging as a crucial field to monitor and manage these risks, but there is still a lack of randomized controlled trials specifically addressing treatment for cardiac issues in childhood cancer survivors, highlighting the need for better identification of high-risk patients and timely intervention.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Pharmacotherapy for Cancer Treatment-Related Cardiac Dysfunction and Heart Failure in Childhood Cancer Survivors.Das, B.[2023]
References
Who Needs Longer Tolvaptan Treatment? [2018]
Effectiveness and adverse events of tolvaptan in octogenarians with heart failure. Interim analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study). [2018]
Pharmacotherapy for Cancer Treatment-Related Cardiac Dysfunction and Heart Failure in Childhood Cancer Survivors. [2023]
Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. [2022]
Tolvaptan for the treatment of hyponatremia and congestive heart failure. [2009]
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