A Study to Learn How Safe Starting Vericiguat at a Dose of 5 Milligrams is in Participants With Chronic Heart Failure With Reduced Ejection Fraction

NCT06195930 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 216832023-507682-25-00
• Study Type: interventional
• Target: 106
• Locations: 7 countries
• Sites: 35

Brief Summary

Researchers are looking for a better way to treat people who have chronic heart failure with reduced ejection fraction. Chronic heart failure with reduced ejection fraction (HFrEF) is a long-term condition that occurs when the heart is too weak to pump enough blood to the rest of the body. This results in a reduced supply of the oxygen that the body requires to function properly. The common symptoms of HFrEF include breathlessness, weakness, fatigue, and swelling in the ankles and legs. If left untreated, heart failure can lead to other serious health problems, including damage to other organs, which may result in hospital stays or even death. Vericiguat is an approved drug for use in people with chronic HFrEF. It works by activating a protein called soluble guanylate cyclase, which helps dilating the blood vessels and in turn improves heart function. Currently, treatment with vericiguat starts at a daily dose of 2.5 milligrams (mg), which increases to 5 mg after 2 weeks. The dose is then increased to the target dose of 10 mg after another 2 weeks. In this study, researchers are trying to learn how well participants can tolerate and how safe it is to start vericiguat at a dose of 5 mg. Starting directly at the 5 mg dose is expected to help reach the target dose of 10 mg faster. Participants will take vericiguat 5 mg as a tablet by mouth once daily along with their regular heart medications. At the start of the study, study doctors will check participants' medical history and perform full health check-ups to confirm if they can take part in the study. Throughout the study, study doctors will monitor participants' previous and current medications, their heart health, and their overall well-being. This will help researchers assess how safe the study drug is and if they experience adverse events. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective of whether they think they are related to the study treatment. Access to study treatment after the end of this study is not planned. Everyone, including study doctors and participants, will know what drug the participants receive during the study. Participants may be in the study for about 4 weeks. Participants may not benefit from the treatment as the study is designed to assess safety and tolerability: the duration of the study is very short and participants will be taking a low dose of vericiguat without moving to the target dose of 10 mg during the study. However, the findings of this study may enable people with chronic HFrEF to safely skip one initial dosing step and reach the target dose of vericiguat faster. Participants may experience medical problems such as low blood pressure, upset stomach, nausea, dizziness, and headache. Researchers will monitor and manage all these, and other, medical problems participants may have during the study.

Conditions

Chronic Heart Failure With Reduced Ejection Fraction

Keywords

HFrEF

Outcome Measures

Primary Outcomes (2)

• Treatment Tolerability: Number of Participants Without Discontinuation of Study Intervention (Incl. Max. 1 Day Interruption) and Without Moderate to Severe Symptomatic Hypotension

  Treatment tolerability, defined as the completion of the two-week 5 mg dose without discontinuation of study intervention (incl. max. 1 day interruption) and without moderate to severe symptomatic hypotension between Visit 1 and Visit 2

  Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)

• Treatment Tolerability: Number of Participants Without Discontinuation of Study Intervention (Max. 2 Day Interruption Included) and Without Moderate to Severe Symptomatic Hypotension

  Treatment tolerability, defined as the completion of the two-week 5 mg dose without discontinuation of study intervention (incl. max. 2 day interruption) and without moderate to severe symptomatic hypotension between Visit 1 and Visit 2

  Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)

Secondary Outcomes (3)

• Number of Participants With Any Adverse Event (AE) Reported Between Visit 1 and Visit 2

  Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)

• Number of Participants With no AE Related to Study Intervention Between Visit 1 and Visit 2

  Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)

• Number of Participants With Continuous Intake of Study Intervention Between Visit 1 and Visit 2 or Restart of Study Intervention After Any Temporary Interruption.

  Between Visit 1 (Day 1) and Visit 2 (Day 14 up to Day 18 if +4 days time window is used)

Study Arms (1)

Overall study

EXPERIMENTAL

At Visit 1 participants will receive 1x 5 mg Vericiguat (BAY1021189) tablet daily (on top of standard of care) for at least 14 days to max 18 days (+4 days time window allowed)

Drug: Vericiguat (BAY1021189) 5 mg

Interventions

Vericiguat (BAY1021189) 5 mg DRUG

Vericiguat (BAY1021189) will be taken as 5 mg tablet 1x daily over at least 14 days up to 18 days (+ 4 days time window allowed)

Overall study

Eligibility Criteria

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

You may qualify if:

• Has an Left ventricle ejection fraction (LVEF) of \<45% assessed within 12 months before Visit 1 by local any imaging method, and no subsequent LVEF measurement \> 45%. The most recent measurement must be used to determine eligibility.
• systolic blood pressure (SBP) ≥ 100 mmHg at screening and Visit 1 (pre-treatment).
• No changes in guideline-directed medical therapy for heart failure (GDMT) dosing (including beta blockers, angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker (ACEI/ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonist (MRAs), hydralazine-nitrate combinations, sodium-glucose cotransporter 2 i(SGLT2) inhibitors, ivabradine, or oral diuretics):
• Within 4 weeks of screening for participants without a heart failure (HF) event ≤6 months prior to screening
• within 2 weeks of screening for participants with a HF event ≤6 months prior to screening
• planned during study participation
• No expected medical procedures to occur 2 weeks before screening or during study participation.
• Participants with ( group 1) OR without (group 2) recent worsening HF event Group 1: History of chronic HF (NYHA class II symptomatic-IV) on GDMT with recent HFevent within 6 months of screening or outpatient IV / SC diuretic use within 3 months before screening.
• OR Group 2: History of chronic HF (NYHA class II symptomatic-IV) on GDMT without recent HF event within 6 months of screening or outpatient intravenous/ subcutaneous (IV / SC) diuretic use within 3 months before screening.

You may not qualify if:

• History of symptomatic hypotension 4 weeks before screening
• Primary valvular heart disease requiring surgical procedure or intervention or has undergone a vascular surgical procedure or intervention within 3months before visit 1
• Hypertrophic cardiomyopathy
• Acute myocarditis or Takotsubo cardiomyopathy
• Awaiting heart transplantation (United Network for Organ Sharing Class 1A /1B or equivalent) or has or anticipates receiving an implanted ventricular assist device, or has received a heart transplant.
• Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia.
• Acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction (NSTEMI), or ST elevation myocardial infarction (STEMI), undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within 3months before Visit 1, or indication for coronary revascularization at the time of treatment assignment.
• Symptomatic carotid stenosis, transient ischemic attack (TIA), or stroke within 3 months before Visit 1.
• History of repaired or unrepaired simple congenital heart disease (e.g., atrial or ventricular septal defects, or patent ductus arteriosus) with ongoing hemodynamically significant residual lesions, or any history of complex congenital heart disease (e.g. tetralogy of Fallot, transposition of the great arteries, single ventricle disease) regardless of repair status.
• Active endocarditis or constrictive pericarditis.
• Hemodynamic instability or hypovolemia within 4 weeks of screening and during the screening period.
• Currently hospitalized.
• estimated glomerular filtration rate (eGFR) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation of \<15 mL/min/1.73 m2 within 30 days before Visit 1 or on chronic dialysis. For participants with multiple eGFR results during screening, the most recent value will be used to determine eligibility.
• Severe hepatic insufficiency defined as albumin to bilirubin ratio (ALBI) Grade 3 or hepatic encephalopathy, or has hepatic laboratory abnormalities (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 ×upper limit of normal (ULN) or total bilirubin ≥2 × ULN). Exceptions for Gilbert's syndrome will be considered. Albumin, ALT, AST, and total bilirubin results within 30 days before Visit 1 may be used for assessment of laboratory abnormalities or the calculation of the ALBI score. For participants with multiple albumin and/or total bilirubin results during screening, the most recent value for each test will be used to calculate ALBI score.
• Malignancy or other noncardiac condition limiting life expectancy to \<3years.

Sponsors & Collaborators

• Bayer: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (35)

Advanced Cardiovascular, LLC - Alexander City

Alexander City, Alabama, 35010, United States

Location

Reid Physician Associates | Cardiology Department

Richmond, Indiana, 47374, United States

Location

Ascension Saint Agnes Heart Care

Baltimore, Maryland, 21229, United States

Location

St. Louis Heart & Vascular, PC

St Louis, Missouri, 63136, United States

Location

Chear Center LLC

New York, New York, 10455, United States

Location

Centro de Investigacion y Prevencion Cardiovascular | Sede Recoleta

Buenos Aires, Ciudad Auton. de Buenos Aires, C1119ACN, Argentina

Location

CEDIC Centro de Investigación Clínica | Buenos Aires, Argentina

CABA, Ciudad Auton. de Buenos Aires, C1018DES, Argentina

Location

Consultorios Integrados Rosario | Instituto Medico de la Fundacion de Estudios Clinicos

Rosario, Santa Fe Province, S2000DEJ, Argentina

Location

Instituto de Cardiologia de Corrientes Juana F. Cabral | Corrientes, Argentina

Corrientes, 3400, Argentina

Location

Centro de Investigaciones Clinicas del Litoral | Santa Fe, Argentina

Santa Fe, S3000FWO, Argentina

Location

Semmelweis Egyetem Belgyógyaszati és Haematológiai Klinika, Kardiológia

Budapest, 1088, Hungary

Location

Eszak-Pesti Centrumkorhaz-Honvedkorhaz

Budapest, 1134, Hungary

Location

Somogy Varmegyei Kaposi Mor Oktato Korhaz

Kaposvár, 7400, Hungary

Location

Coromed Smo Kft

Pécs, 7623, Hungary

Location

Tolna Varmegyei Balassa Janos Korhaz

Szekszárd, 7100, Hungary

Location

Complex Rendelo Med Zrt.

Székesfehérvár, 8000, Hungary

Location

ASST Papa Giovanni XXIII

Bergamo, Lombardy, 24127, Italy

Location

ASST Spedali Civili di Brescia

Brescia, Lombardy, 25123, Italy

Location

IRCCS Centro Cardiologico Monzino

Milan, Lombardy, 20138, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, Lombardy, 27100, Italy

Location

Malopolskie Centrum Sercowo-Naczyniowe PAKS

Chrzanów, 32-500, Poland

Location

Vita Longa Sp. z o.o.

Katowice, 40-748, Poland

Location

Centrum Medyczne Zdrowa

Krakow, 31-216, Poland

Location

Clinical Best Solutions Sp. Z O.O. Sp.K.

Lublin, 20-011, Poland

Location

NZOZ "Twoja Przychodnia" Sp. z o.o.

Lublin, 20-857, Poland

Location

IRMED Osrodek Badan Klinicznych

Piotrkow Trybunalski, 97-300, Poland

Location

Clinical Best Solutions Sp. Z O.O. Sp.K.

Warsaw, 00-710, Poland

Location

Hospital Clinico Universitario de Santiago de Compostela | Cardiology Department

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital del Mar | Cardiology Department

Barcelona, 08003, Spain

Location

Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology Department

Barcelona, 08907, Spain

Location

Hospital Ramon y Cajal | Cardiology - Research Unit

Madrid, 28034, Spain

Location

Hospital la Paz

Madrid, 28046, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Capio Citykliniken - Hjartmottagning

Lund, 222 21, Sweden

Location

Karolinska Universitetssjukhuset

Stockholm, 17176, Sweden

Location

Related Links

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MeSH Terms

Interventions

vericiguat

Limitations and Caveats

Study Design: This analysis is based on a single-arm design, which may limit the generalizability of the findings. The absence of a control group restricts our ability to make definitive conclusions about the tolerability and safety of starting vericiguat at 5 mg/day to standard care or placebo. The results are based on descriptive statistics, which provide a summary of the data but do not infer causality or generalizability to a broader population.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multi-center, single arm, open label study of vericiguat initiation at 5 mg in HFrEF patients with EF \<45%. The total study duration is approximately 4 weeks, including a 2-week screening period and a 2-week treatment period . Screening: Approximately 120 participants will be screened to achieve at least 100 participants who are assigned to study intervention and complete the treatment period of up to 2 weeks. Participants will undergo a screening visit to assess eligibility. Eligible participants must wait a mandatory 2 weeks before returning for Visit 1 in order to be clinically and hemodynamically stable. Treatment: At Visit 1, participants will receive vericiguat 5 mg (on top of standard of care) with directions to take once daily for 2 weeks. Participants will return for a study visit (Visit 2) after 2 weeks of treatment. Unscheduled visits may be utilized between Visits 1 and 2 at the discretion of the investigator for AE review and reporting.

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: January 8, 2024
• Study Start: April 18, 2024
• Primary Completion: July 29, 2024
• Study Completion: July 29, 2024
• Last Updated: September 25, 2025
• Results First Posted: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); PL (7); US (5); HU (6); IT (4); ES (6); AR (5)