Post-COVID ME/CFSPhase 2NCT05697640
Study to Investigate Improvement in Physical Function in SF-36 With Vericiguat Compared With Placebo in Participants With Post-COVID-19 Syndrome
A Phase 2 study testing Vericiguat Oral Tablet in people with Post-COVID ME/CFS, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Post-COVID ME/CFS
- What is being tested?
- Vericiguat Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteGermany
- Study dates
- 22 Jun 2023to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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 %):
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- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Charité - Universitätsmedizin Berlin
Berlin, State of Berlin, 10117
About this study
Official title: A Parallel-group Treatment, Phase 2a, Double-blind, Placebo-controlled 2-arm Study to Show Improvement of Physical Function in SF-36 (SF-36-PF) in Participants Treated With Vericiguat Compared to Placebo Tablets in Male and Female Participants Aged 18-50 Years With Post-COVID-19 Syndrome Without (PCS) or With (PCS/CFS) Fulfillment of ME/CFS Criteria (VERI-LONG).
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.
Read the 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
- Being tested
- Vericiguat Oral Tablet
- Keywords
- Post-COVID Syndrome, Long COVID, Chronic Fatigue Syndrome
- Medical subject headings
- Post-Acute COVID-19 Syndrome, Fatigue Syndrome, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vericiguat Oral TabletDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Vericiguat Oral Tablet | Active comparator | 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). Receives: Drug: Vericiguat Oral Tablet |
| Placebo Oral Tablet | Placebo comparator | 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. Receives: Drug: Vericiguat Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Physical Function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36)
The Short Form 36 Health Survey (SF-36) is an established and widely used health-related quality of life measure. The Physical Function (PF) domain asks patients to report limitations on ten mobility activities, such as walking specified distances, carrying groceries, and bathing or dressing. Scores are weighted and transformed into a scale ranging from 0 (greatest possible health restrictions, i.e., severe disability) to 100 (no health restrictions). An intra-patient change of 10 points in SF-36-PF from baseline to week ten is considered clinically meaningful.
Measured: 10 weeks after first IMP intake
Secondary outcomes (16)
Difference in responder rate in Physical Function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36) comparing Vericiguat with placebo
Occurrence of responders in patients that receive Vericiguat compared with placebo. Responders are defined as an intra-patient 10-point increase in SF-36-PF from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in other sub-domains of the Short Form 36 Health Survey Questionnaire (SF-36) comparing Vericiguat with placebo
Intra-patient change in other SF-36 subdomains from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in fatigue as measured by the Fatigue Severity Score (FSS)
The Fatigue Severity Scale (FSS) is a 9-item scale that measures the severity of fatigue and its effect on a person's activities and lifestyle. Answers are scored on a seven-point scale (1 = strongly disagree; 7 = strongly agree). Thus, the minimum score is 9 (no fatigue), and the highest is 63 (heavy fatigue). Intra-patient change in fatigue severity from baseline to week 10 will be documented as indexed by the FSS.
Measured: 10 weeks after first IMP intake
Improvement in severity of muscle pain and headache as measured by the Canadian Consensus Criteria (CCC) symptom score
The Canadian Consensus Criteria (CCC) Symptom Score quantifies ME/CFS symptoms. Its score ranges from 1 (no symptoms) to 10 (extreme symptoms). Intra-patient change in muscle pain and headache from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in symptoms of myalgic encephalomyelitis (ME)/ chronic fatigue syndrome (CFS) as measured by Canadian Consensus Criteria (CCC) Symptom Score
Intra-patient change in ME/CFS symptoms from baseline to week 10 will be documented as indexed by the CCC Symptom Score.
Measured: 10 weeks after first IMP intake
Improvement in functional disability as measured by the Bell disability scale
The Bell disability scale is a standard assessment in ME/CFS that evaluates functional ability in adult ME/CFS patients. Eleven statements describe patient status such as level of symptoms at rest, level of symptoms with exercise, activity level, and ability to perform work, travel and self care. Its score ranges from 0 (bedridden) to 100 (no symptoms). Intra-patient change in Bell score from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in symptoms of autonomic dysfunction as measured by the Composite Autonomic Symptom Score (COMPASS-31)
The Composite Autonomic Symptom Score (COMPASS-31) is a refined, internally consistent, and markedly abbreviated quantitative measure of autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, applies a much-simplified scoring algorithm, and is suitable for widespread use in autonomic research and practice. It evaluates six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains. The score ranges from 0 (no symptoms) to 100 (strong autonomic dysfunction). Intra-patient change in autonomic dysfunction from baseline to week ten will be documented as indexed by the COMPASS-31.
Measured: 10 weeks after first IMP intake
Improvement in disease severity based on self- reported symptoms as measured by the Munich Berlin Symptom Questionnaire (MBSQ)
The Munich Berlin Symptom Questionnaire (MBSQ) is a questionnaire for ME/CFS that captures the IOM and CCC diagnostic criteria as well as a total of 44 symptoms from 8 domains on a scale of 0 - 4 for frequency and severity. From this, a score for total symptom severity ranging from 0 (not present) to 352 (very severe) is calculated. Intra-patient change in MBSQ score from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in disease severity based on self- reported symptoms as measured by the Munich Long Covid Symptom Questionnaire (MLCSQ)
The Munich Long Covid Symptom Questionnaire (MLCSQ) is a long covid questionnaire that measures a total of 83 symptoms from 13 domains on a scale of 1-3 for frequency and severity. This results in a score for total symptom severity ranging from 83 (mild) to 496 (severe). Intra-patient change in MLCSQ score from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in post exertional malaise (PEM) frequency, strength and severity as measured by the PEM questionnaire
The PEM questionnaire determines frequency (from 0 to 20 points, higher scores equate to greater frequency), severity (from 0 to 20 points, higher scores equate to greater severity), and length (from 0 to 6 points, higher scores equate to longer duration) of PEM. Intra-patient change in PEM score from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in muscle fatigue measured by the repetitive hand grip strength test (HGS)
Intra-patient change in hand grip strength (HGS) from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in orthostatic intolerance measured by the passive standing test
Intra-patient change in blood pressure, sitting and standing heart rate, and delta heart rate from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement of endothelial cell function as assessed using EndoPAT
Intra-patient change in vascular regulation as indexed by the reactive hyperemia index (RHI) from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in cognitive function measured by the Symbol Digit Modalities Test (SDMT)
The Symbol Digit Modalities Test (SDMT) is a screening instrument commonly used to assess neurological dysfunction. It detects cognitive impairment as well as changes in cognitive functioning over time and in response to treatment. The scores range between 0 and 110 (higher scores equate to greater cognitive functioning). Intra-patient change in cognitive score from baseline to week ten.
Measured: 10 weeks after first IMP intake
Improvement in ET-1 serum levels
Intra-patient change in ET-1 level from baseline to week ten.
Measured: 10 weeks after first IMP intake
Difference of occurring AE and SAE comparing Vericiguat with placebo (IMP safety).
Occurrence of IMP side and adverse effects, assessed with AE, SAE and SUSAR reports
Measured: 10 weeks after first IMP intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2023
- Study start22 Jun 2023
- Primary completion1 Apr 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-COVID ME/CFSStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two-arm parallel-group, randomized, placebo-controlled, double-blind, single-centre clinical trial in participants with post-COVID syndrome with and without ME/CFS.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Judith Bellmann-Strobl, Charite University, Berlin, Germany
- Investigators
- Judith Bellmann-Strobl, MD, Principal investigator, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05697640
- Sponsor's protocol ID
- VERI-LONG
- Other IDs
- 01EP2201
- Status last verified
- Jan 2026
- First submitted
- 23 Jan 2023
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 32222134
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Parallel-group Treatment, Phase 2a, Double-blind, Placebo-controlled 2-arm Study to Show Improvement of Physical Function in SF-36 (SF-36-PF) in Participants Treated With Vericiguat Compared to Placebo Tablets in Male and Female Participants Aged 18-50 Years With Post-COVID-19 Syndrome Without (PCS) or With (PCS/CFS) Fulfillment of ME/CFS Criteria (VERI-LONG).
- ClinicalTrials.gov ID
- NCT05697640
- Acronym / sponsor ID
- VERI-LONG
- Conditions
- Post-COVID ME/CFS
- Keywords
- Post-COVID Syndrome, Long COVID, Chronic Fatigue Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 22 Jun 2023 (actual)
- Primary completion
- 1 Apr 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 26 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two-arm parallel-group, randomized, placebo-controlled, double-blind, single-centre clinical trial in participants with post-COVID syndrome with and without ME/CFS.
| Arm | Type | Receives |
|---|---|---|
| Vericiguat Oral Tablet | Active comparator | Drug: Vericiguat Oral TabletTested 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). |
| Placebo Oral Tablet | Placebo comparator | Drug: Vericiguat Oral TabletComparator 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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))]
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vericiguat Oral TabletThe 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). | Drug | Placebo Oral Tablet, Vericiguat Oral Tablet |
Primary outcome
Improvement in Physical Function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36)
Time frame: 10 weeks after first IMP intake
The Short Form 36 Health Survey (SF-36) is an established and widely used health-related quality of life measure. The Physical Function (PF) domain asks patients to report limitations on ten mobility activities, such as walking specified distances, carrying groceries, and bathing or dressing. Scores are weighted and transformed into a scale ranging from 0 (greatest possible health restrictions, i.e., severe disability) to 100 (no health restrictions). An intra-patient change of 10 points in SF-36-PF from baseline to week ten is considered clinically meaningful.
16 secondary outcomes
Difference in responder rate in Physical Function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36) comparing Vericiguat with placebo
Time frame: 10 weeks after first IMP intake
Improvement in other sub-domains of the Short Form 36 Health Survey Questionnaire (SF-36) comparing Vericiguat with placebo
Time frame: 10 weeks after first IMP intake
Improvement in fatigue as measured by the Fatigue Severity Score (FSS)
Time frame: 10 weeks after first IMP intake
Improvement in severity of muscle pain and headache as measured by the Canadian Consensus Criteria (CCC) symptom score
Time frame: 10 weeks after first IMP intake
Improvement in symptoms of myalgic encephalomyelitis (ME)/ chronic fatigue syndrome (CFS) as measured by Canadian Consensus Criteria (CCC) Symptom Score
Time frame: 10 weeks after first IMP intake
Improvement in functional disability as measured by the Bell disability scale
Time frame: 10 weeks after first IMP intake
Improvement in symptoms of autonomic dysfunction as measured by the Composite Autonomic Symptom Score (COMPASS-31)
Time frame: 10 weeks after first IMP intake
Improvement in disease severity based on self- reported symptoms as measured by the Munich Berlin Symptom Questionnaire (MBSQ)
Time frame: 10 weeks after first IMP intake
Improvement in disease severity based on self- reported symptoms as measured by the Munich Long Covid Symptom Questionnaire (MLCSQ)
Time frame: 10 weeks after first IMP intake
Improvement in post exertional malaise (PEM) frequency, strength and severity as measured by the PEM questionnaire
Time frame: 10 weeks after first IMP intake
Improvement in muscle fatigue measured by the repetitive hand grip strength test (HGS)
Time frame: 10 weeks after first IMP intake
Improvement in orthostatic intolerance measured by the passive standing test
Time frame: 10 weeks after first IMP intake
Improvement of endothelial cell function as assessed using EndoPAT
Time frame: 10 weeks after first IMP intake
Improvement in cognitive function measured by the Symbol Digit Modalities Test (SDMT)
Time frame: 10 weeks after first IMP intake
Improvement in ET-1 serum levels
Time frame: 10 weeks after first IMP intake
Difference of occurring AE and SAE comparing Vericiguat with placebo (IMP safety).
Time frame: 10 weeks after first IMP intake
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Background: PubMed 32222134Armstrong 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judith Bellmann-Strobl, MD principal investigator
Charite University, Berlin, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vericiguat Oral Tablet in people with Post-COVID ME/CFS, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in Physical Function (PF) as measured by the Short Form 36 Health Survey Questionnaire (SF-36) (time frame: 10 weeks after first IMP intake). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05697640, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.