Study to Investigate Improvement in Physical Function in SF-36 With Vericiguat Compared With Placebo in Participants With Post-COVID-19 Syndrome

NCT ID: NCT05697640

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-22
• Study Completion Date: 2026-12-31

Brief Summary

The goal of this clinical trial is to evaluate the therapeutic value of an approved drug (Vericiguat) in patients with post-COVID-19 syndrome, who suffer from profound tiredness or fatigue, regardless of bed rest.The main questions it aims to answer are: • Does Vericiguat relieve fatigue and/or other symptoms associated with post-COVID-19 syndrome? • What are the side effects of Vericiguat in this patient population; and how common are they?

Participants will be asked to participate for approx. 18 weeks. After screening, participants will receive assigned intervention of either 10 weeks of treatment with Vericiguat or matching placebo tablet, followed by 30 day follow-up period. Every participant will undergo trial, cardiovascular safety, and monitoring assessments.

The results of this study will provide information on whether Vericiguat can alleviate PCS-related symptoms as well as insights into the pathophysiological processes of PCS, which in turn can help to develop therapies.

Detailed Description

Although of high socioeconomic relevance, the pathomechanisms of post-COVID-19 syndrome (PCS) are not well understood and there is no established therapy. Preliminary evidence suggests that systemic tissue and organ hypoperfusion, resulting from impaired microvascular blood flow secondary to chronic endothelial dysfunction (ED), plays a key role in many symptoms.

The objective is to demonstrate improvement in physical function measured using the short form-36 health questionnaire (SF-36) in patients with post-COVID-19 syndrome with or without fulfillment of ME/CFS criteria treated with Vericiguat compared with placebo. Vericiguat is a drug that bridges endothelial dysfunction to improve microvascular perfusion and tissue and organ blood flow.

This is a two-arm parallel-group, randomized, placebo-controlled, double-blind, single-centre clinical trial in participants with PCS and PCS/CFS. Patients participate for approx. 18 weeks. Participants will be stratified according to diagnosis (with vs. without ME/CFS) and sex, and randomly assigned 1:1 after a screening phase of up to 28 days to receive assigned intervention of either 10 weeks of treatment with Vericiguat (including titration phase) or placebo, followed by 30 days follow-up period. One group receives a tablet of Vericiguat once daily for 10 weeks with a dosage titration to tolerated dose of 2.5 mg for 2 weeks, 5 mg for 2 weeks, 10 mg for 6 weeks. The other group receives a matching placebo tablet once daily for 10 weeks with the same titration regimen to ensure blinding. The starting dose is 2.5 mg Vericiguat or matching placebo, once daily, and a controlled and blood pressure-tolerated titration regimen will be used to achieve the anticipated target dose of 10 mg Vericiguat or matching placebo. Every participant will undergo trial, cardiovascular safety, and monitoring assessments. During the screening visit, the study team i) records the patient's medical history, ii) checks the in- and exclusion criteria, iii) performs a medical check-up, iv) performs an echocardiogram, and v) measures the patient's vital parameters. In female participants, a pregnancy test is carried out 5 times during the study.

The results of this study will provide information on whether Vericiguat can alleviate PCS-related symptoms such as fatigue, cognitive impairment, and impaired physical function (e.g., walking, stair climbing) and/or modulate paraclinical markers such as parameters of endothelial function. Moreover, the clinical trial will provide insights into the pathophysiological processes of PCS, which in turn can help to elucidate the disease etiology and to develop effective therapies.

Conditions

Post-COVID ME/CFS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vericiguat Oral Tablet

Tested IMP: Vericiguat (film-coated tablet). Authorization status: Not authorised in this targeted therapeutic indication; Vericiguat is authorized for the dosages that will be administered in this trial for another indication. The tablets used in this trial are no trade product, but a special trial product produced and provided by the marketing authorization holder Bayer.

Administration: Once daily (oral). Planned dosage: Three different dosages starting with 2.5 mg for two weeks, followed by 5 mg for two weeks and 10 mg for six weeks. The general IMP titration regimen was investigated and proven to be safe (max. dosages 10 mg/day) in patients with heart failure and reduced ejection fraction (Armstrong et al., 2020).

Group Type: ACTIVE_COMPARATOR

Vericiguat Oral Tablet

Intervention Type: DRUG

The treatment period includes ten weeks of daily vericiguat or placebo intake (depending on randomization) and a 30-day follow-up period (no vericiguat/placebo intake).

Placebo Oral Tablet

Comparator IMP: Placebo (film-coated tablet). Authorization status: Not authorised. The tablets used in this trial are no trade product, but a special trial product produced and provided by the marketing authorization holder Bayer.

Administration: Once daily (oral). Planned dosage: Three different dosages starting with 2.5 mg for two weeks, followed by 5 mg for two weeks and 10 mg for six weeks to have identical conditions to verum.

Group Type: PLACEBO_COMPARATOR

Vericiguat Oral Tablet

Intervention Type: DRUG

The treatment period includes ten weeks of daily vericiguat or placebo intake (depending on randomization) and a 30-day follow-up period (no vericiguat/placebo intake).

Interventions

Vericiguat Oral Tablet

The treatment period includes ten weeks of daily vericiguat or placebo intake (depending on randomization) and a 30-day follow-up period (no vericiguat/placebo intake).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female adult who is 18-50 years old
• Confirmed (PCR or serology), non-hospitalized, mild to moderate acute COVID-19 cases according to WHO criteria with proven chronic ED and either: ME/CFS Canadian Consensus Criteria (CCC) with post exertional malaise (PEM) 2 - 14 hours = PCS or ME/CFS CCC criteria with PEM > 14 hours = PCS/CFS
• Ongoing symptoms of PCS or PCS/CFS for ≥ 6 months
• Bell Score: 30-60
• Evidence for endothelial dysfunction (ED) [as indicated by reactive hyperemia index (RHI) < 1.8 and/or ET-1 level > 90 percentile of healthy age- and gender matched controls or muscle fatigue (below cut-off values of area under the curve reference values for age-matched healthy controls and/or pathological optical coherence tomography angiography (OCTA))]
• For female subjects: Confirmed post-menopausal state (defined as amenorrhea for at least 12 months) or for women of childbearing potential: Negative highly sensitive urine or serum pregnancy test before inclusion/randomisation and practicing a highly effective birth control method (failure rate of less than 1 %):

• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral/intravaginal/transdermal), or
• progestogen-only hormonal contraception associated with inhibition of ovulation (oral/injectable/implantable), or
• intrauterine device, or
• intrauterine hormone-releasing system, or
• bilateral tubal occlusion, or
• vasectomised partner, or
• heterosexual abstinence.

Exclusion Criteria

• COVID-19 vaccination within the last 4 weeks before inclusion
• Pre-COVID history of chronic fatigue syndrome or other fatigue syndromes that are due to associated diseases (e.g., cancer, autoimmune diseases [patients with a preexisting Hashimoto thyroiditis and/or fibromyalgia without fatigue syndromes can be included])
• Concomitant use of Vericiguat due to other diseases
• Contraindications against IMP
• Concurrent or anticipated concomitant use of PDE-5 inhibitors such as vardenafil, tadalafil, and sildenafil, nitrates, or sGC-stimulators
• Use of other sGC stimulators, e.g., riociguat
• Hypersensitivity to the active substance or any of the other ingredients
• Systolic blood pressure: < 100 mmHg at screening
• Known SARS-CoV-2 infection-related organ damage/comorbidity
• Severe renal or hepatic insufficiency
• Pregnancy or breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Judith Bellmann-Strobl

Senior physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Judith Bellmann-Strobl, MD

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Locations

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, Germany

Countries

Germany

References

Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, Lam CSP, Ponikowski P, Voors AA, Jia G, McNulty SE, Patel MJ, Roessig L, Koglin J, O'Connor CM; VICTORIA Study Group. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020 May 14;382(20):1883-1893. doi: 10.1056/NEJMoa1915928. Epub 2020 Mar 28.

Reference Type: BACKGROUND

PMID: 32222134 (View on PubMed)

Other Identifiers

01EP2201

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

VERI-LONG

Identifier Type: -

Identifier Source: org_study_id