Tovinontrine for Heart Failure
(Cycle-1-REF Trial)
Recruiting in Palo Alto (17 mi)
+97 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Cardurion Pharmaceuticals, Inc.
Must be taking: Guideline-directed HF therapy
Disqualifiers: Recent HF exacerbation, Acute coronary syndrome, others
Prior Safety Data
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?
The research does not provide direct evidence for Tovinontrine, but studies on a similar drug, tolvaptan, show it can improve symptoms in heart failure patients by increasing fluid loss and improving edema (swelling) and sodium levels.
12345Eligibility 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;
I am 18 years old or older.
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;
Trial 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
Participant Groups
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.
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
Research Locations NearbySelect from list below to view details:
Cardurion Investigative SiteJacksonville, FL
Cardurion Investigative SiteVan Nuys, CA
Cardurion Investigative SiteMiami, FL
Cardurion Investigative SiteMcKinney, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Cardurion Pharmaceuticals, Inc.Lead Sponsor
References
Who Needs Longer Tolvaptan Treatment? [2018]The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been approved for heart failure patients with volume overload in Japan. In this study (SMILE study), we investigated patient characteristics and effectiveness in both a 14 days and shorter treated group (14DS) and 15 days and longer treated group (15DL). The results showed that the patients in the 15DL group had low cardiac output with intensive diuretic administration (ie, diuretic resistance). The congestive symptoms were greatly improved within 14 days of treatment in both the 14DS and 15DL groups. Further improvements in lower limb edema, pulmonary congestion, dyspnea, third sound, and rales after 2 weeks were statistically significant in the 15DL group, but the amount of improvement was subtle and the 15DL group might have consisted of a considerable number of "non-responders". Therefore, identifying "responders" by biomarkers and conducting a prospective randomized study is required to validate our findings.
Effectiveness and adverse events of tolvaptan in octogenarians with heart failure. Interim analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study). [2018]The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been found to improve symptoms in patients with congestive heart failure. In this study (SMILE study), we administered tolvaptan to patients aged ≥ 80 years with heart failure accompanied by congestive symptoms and compared its effectiveness and safety profiles in this group with those in patients
Pharmacotherapy for Cancer Treatment-Related Cardiac Dysfunction and Heart Failure in Childhood Cancer Survivors. [2023]The number of childhood cancer survivors is increasing rapidly. According to American Association for Cancer Research, there are more than 750,000 childhood cancer survivors in the United States and Europe. As the number of childhood cancer survivors increases, so does cancer treatment-related cardiac dysfunction (CTRCD), leading to heart failure (HF). It has been reported that childhood cancer survivors who received anthracyclines are 15 times more likely to have late cancer treatment-related HF and have a 5-fold higher risk of death from cardiovascular (CV) disease than the general population. CV disease is the leading cause of death in childhood cancer survivors. The increasing need to manage cancer survivor patients has led to the rapid creation and adaptation of cardio-oncology. Cardio-oncology is a multidisciplinary science that monitors, treats, and prevents CTRCD. Many guidelines and position statements have been published to help diagnose and manage CTRCD, including those from the American Society of Clinical Oncology, the European Society of Cardiology, the Canadian Cardiovascular Society, the European Society of Medical Oncology, the International Late Effects of Childhood Cancer Guideline Harmonization Group, and many others. However, there remains a gap in identifying high-risk patients likely to develop cardiomyopathy and HF in later life, thus reducing primary and secondary measures being instituted, and when to start treatment when there is echocardiographic evidence of left ventricular (LV) dysfunctions without symptoms of HF. There are no randomized controlled clinical trials for treatment for CTRCD leading to HF in childhood cancer survivors. The treatment of HF due to cancer treatment is similar to the guidelines for general HF. This review describes the latest pharmacologic therapy for preventing and treating LV dysfunction and HF in childhood cancer survivors based on expert consensus guidelines and extrapolating data from adult HF trials.
Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. [2022]In this study, we evaluated the effects of tolvaptan (OPC-41061), a novel, oral, nonpeptide vasopressin V2-receptor antagonist in patients with chronic heart failure (CHF).
Tolvaptan for the treatment of hyponatremia and congestive heart failure. [2009]Tolvaptan is an oral, once-daily nonpeptide arginine vasopressin V(2)-receptor antagonist under development for the treatment of hyponatremia and congestive heart failure. In Phase II clinical trials, tolvaptan, in addition to standard therapy, increased fluid loss, resulting in decreased body weight and improved edema and serum sodium without affecting blood pressure, heart rate or renal function in patients with heart failure. The compound appeared to be well tolerated and dose-dependent adverse events were generally realated to its pharmacological activity, such as thirst and dry mouth. In patients with hyponatremia, tolvaptan appears to be more effective than fluid restriction at improving sodium levels without an increase in adverse events. An international Phase III outcome study; Efficacy of Vasopressin antagonism in hEaRt failurE outcome Study with Tolvaptan (EVEREST), evaluating the long-term efficacy and safety of tolvaptan in patients hospitalized with worsening heart failure, is currently ongoing.