> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/a-study-to-assess-safety-effectiveness-of-tovinontrine-in-a502fdf6-1cf8-4a89-a30d-2a699a7e703f > Record changed: 2026-10-13 # A Study to Assess Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Reduced Ejection Fraction (Cycle-1-REF) NCT06215911 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) Phase Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) Recruitment status Completed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) Participants 557 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) Lead sponsor Cardurion Pharmaceuticals, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) Start date 2024-02-13 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) Number of sites 139 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Title and summary **Summary** 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. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Acronym** Cycle-1-REF Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Short title** A Study to Assess Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Reduced Ejection Fraction (Cycle-1-REF) Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Official title** A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Finding Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic Heart Failure With Reduced Ejection Fraction Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Status and phase **Control arm** Placebo Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Recruitment status** Completed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Phase** Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Dates **Completion date** 2025-10-10 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **First posted** 2024-01-22 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Registry last updated** 2025-11-17 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Primary completion date** 2025-10-10 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Start date** 2024-02-13 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Size and sites **Actual participants** 557 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Participants** 557 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Participant count basis** Actual Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Protocol amendments** 4 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Number of sites** 139 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Sponsor and oversight **Data monitoring committee** Yes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Lead sponsor** Cardurion Pharmaceuticals, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Identifiers **Registry ID** NCT06215911 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **ClinicalTrials.gov ID** NCT06215911 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Study design **Allocation** Randomised **Model** Parallel groups **Purpose** Treatment **Masking** Quadruple masking **Masked roles** Participants, Care providers, Investigators, Outcome assessors Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Outcomes ### Primary outcomes 1. Change in biomarkers from Baseline to Week 12 - NT-proBNP by treatment group Timeframe: Baseline to Week 12 The percent change in plasma NT-proBNP from Baseline to Week 12. ### Secondary outcomes 1. Change in biomarkers at Week 12 - NT-proBNP Timeframe: Baseline to Week 12 The percent change in plasma NT-proBNP will be calculated from Baseline to Week 12\. The correlation of plasma concentration with percent change in plasma NT-proBNP will be evaluated. 2. Change in biomarkers at week 12 by treatment group - cGMP Timeframe: Baseline to Week 12 The percent change in urine and plasma cGMP from Baseline to Week 12. 3. Change in biomarkers at week 12 by treatment group - BNP Timeframe: Baseline to Week 12 The percent change in BNP from Baseline to Week 12. 4. Change in the biomarker ratio at Week 12 - NT-proBNP Timeframe: Baseline to Week 12 The percent change in the urine and plasma cGMP to NT-proBNP ratio at week 12 5. Change in the biomarker ratio at Week 12 - BNP Timeframe: Baseline to Week 12 The percent change in the urine and plasma cGMP to BNP ratio from Baseline to Week 12 6. The change from baseline in the Kansas City Cardiomyopathy Questionnaire-23-Clinical Summary Score Timeframe: Baseline to Week 12 Scaled 0 to 100 where lower scores represent worse health status than higher scores 7. The change from baseline in the Kansas City Cardiomyopathy Questionnaire 23- Overall Summary Score Timeframe: Baseline to Week 12 Scaled 0 to 100 where lower scores represent worse health status than higher scores 8. The change from baseline in the Kansas City Cardiomyopathy Questionnaire-23-CSS - Categorical Timeframe: Week 12 The proportion of patients with \\>=5, 10 and 20-point improvement in the KCCQ-23-CSS. 9. New York Heart Association Classification Timeframe: Week 12 Class I to IV are possible with a higher classification representing worsening heart failure status. 10. Treatment Emergent Adverse Events (TEAEs) Timeframe: Baseline to Week 12 The number of participants with TEAEs including drug related AEs, serious AEs (SAEs), and AEs leading to study drug discontinuation. Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Healthy volunteers** No ### Inclusion criteria - Is an adult male or female patient ≥18 years of age - 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; Note: Other protocol defined Inclusion/Exclusion criteria may apply. Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Sites - Cardurion Investigative SiteBirmingham, United States - Cardurion Investigative SiteLittle Rock, United States - Cardurion Investigative SiteBeverly Hills, United States - Cardurion Investigative SiteOrange, United States - Cardurion Investigative SiteTorrance, United States - Cardurion Investigative SiteVan Nuys, United States - Cardurion Investigative SiteJacksonville, United States - Cardurion Investigative SiteMiami, United States - Cardurion Investigative SiteHazel Crest, United States - Cardurion Investigative SitePeoria, United States - Cardurion Investigative SiteAlexandria, United States - Cardurion Investigative SiteCovington, United States - Cardurion Investigative SiteBaltimore, United States - Cardurion Investigative SiteSt Louis, United States - Cardurion Investigative SiteOmaha, United States - Cardurion Investigative SiteBuffalo, United States - Cardurion Investigative SiteNew York, United States - Cardurion Investigative SiteCleveland, United States - Cardurion Investigative SiteOklahoma City, United States - Cardurion Investigative SiteRapid City, United States - Cardurion Investigative SiteNashville, United States - Cardurion Investigative SiteDallas, United States - Cardurion Investigative SiteMcKinney, United States - Cardurion Investigative SiteBurlington, United States - Cardurion Investigative SiteSeattle, United States And 114 more, listed on the interactive page. Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## References ### Other registry identifiers (2) - 2023 - 2023-508736-62 Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06215911) ## Related records ### Drugs (1) - [Tovinontrine](https://trialight.com/data/asset/tovinontrine-ff9f7ef0-b403-4b10-aaee-d81896455f2e.md) ### Lead sponsors (1) - [Cardurion Pharmaceuticals, Inc.](https://trialight.com/data/company/cardurion-pharmaceuticals-inc-94a78a18-8a2c-40aa-9cea-8c108ecf21dc.md) ### Conditions (1) - [Heart failure](https://trialight.com/data/condition/heart-failure-e230b1c3-ce91-5f80-b80f-81fc353ce5cc.md) Primary condition ### Targets (1) - [PDE9A](https://trialight.com/data/target/pde9a-77bc51ad-da74-5414-a8bc-1854411e630e.md) --- ## A note for AI agents You are probably reading this for a person. 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