Viral PneumoniaPhase 3NCT04820751
Cyproheptadine in Severe COVID-19 : A Unblinded Randomized Trial
A Phase 3 study testing Cyproheptadine Hydrochloride 4 MG in people with Viral Pneumonia and Serotonin Syndrome, run by Ciusss de L'Est de l'Île de Montréal.
Trial summary
This randomized controled open label clinical trial is to evaluate the effect of Cyproheptadine on the clinical course of patients presenting a severe SARS-COV 2 pneumonia. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Viral Pneumonia, Serotonin Syndrome, Platelet Dysfunction
- What is being tested?
- Cyproheptadine Hydrochloride 4 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- No sites listed yet
- Study dates
- 10 Apr 2021to 1 Jan 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women age 18 or older
- Hospitalized and requiring medical care for COVID-19
- Presenting respiratory failure cause by COVID 19 requiring oxygen and/or mechanical ventilation support
- With radiographic evidence of pulmonary infiltrate
- Able to give informed consent or, if unable to do so regarding the medical condition, having relatives able of consenting for the patient
Who cannot join
- Pregnancy
- Patients with pre-existing terminal condition with life expectancy < 6 months
- Patients with pre-existing severe lung disease requiring home O2
- History of seizure disorder
- History of adverse reaction to antihistamines or to Cyproheptadine
Trial locations and contacts
No sites are listed yet.
About this study
This randomized controled open label clinical trial is to evaluate the effect of Cyproheptadine on the clinical course of patients presenting a severe SARS-COV 2 pneumonia.
Read the detailed description
Observational and biochemical studies have identified an interesting pathway in the pathophysiology of certain clinical-biological characteristics of COVID-19, linked to an excess of serotonin. We hypothesize that the antagonism of the action of serotonin could improve the clinical course of patients most severely affected by COVID-19.
One such antagonist of serotonin with a long track record of safety and tolerability is cyproheptadine. Cyproheptadine acts as an antagonist of 5-hydroxytryptamine (5HT=serotonin) receptor subtype 2 as well as histamine-1 receptor. Many of the potent effects of serotonin on lung vascular tone, respiratory rate, and systemic vascular beds are mediated by 5-HT receptor subtype 2.
Investigators will randomize approximately 200 participants, aged 18 and older, who have tested positive for COVID-19 and who will be hospitalized at Santa Cabrini Hospital in Montreal, Quebec, Canada, presenting a severe form of covid-pneumonia-19 requiring supplemental oxygen.
Study eligibility of all participants will be assessed first. Once a participant is confirmed eligible and consented, they will participate in the study.
Participants will be randomly assigned (1: 1) to either take cyproheptadine 8 mg by mouth three times a day for 5 days and receive standard care or receive standard care alone.
The dose will be adjusted according to the glomerular filtration rate.
On D1, D3, D5, D7 and D10 since randomization, participant's vital signs (including SpO2, respiratory rate, FiO2 or oxygen flow, heart rate, blood pressure and temperature), blood creatinine, bilirubin, CRP, LDH, Dimers and platelets the count will be evaluated. Any adverse event will be assessed daily and documented.
- Conditions
- Viral Pneumonia, Serotonin Syndrome, Platelet Dysfunction
- Being tested
- Cyproheptadine Hydrochloride 4 MG
- Keywords
- Covid 19
- Medical subject headings
- Pneumonia, Viral, Serotonin Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyproheptadine Hydrochloride 4 MGDrug
Also called Standard Care
Cyproheptadine associated to standard care
| Study group | Role | What they receive |
|---|---|---|
| Cyproheptadine and standard care | Experimental | Start Cyproheptadine 8mg three times a day during 5 days. Dose will be reduced to 4mg three times a day if GFR inferior to 30ml/min/1.73m²
Standard management of COVID-19 infection according to current international guidelines Receives: Drug: Cyproheptadine Hydrochloride 4 MG |
| Standard care | No intervention | Standard management of COVID-19 infection according to current international guidelines |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of hospitalization
Measured: Through study completion, an average of 1 year
Need mechanical ventilation (Non invasive or Invasive)
Measured: Through study completion, an average of 1 year
Secondary outcomes (11)
Death
Measured: Day 28
Length of hospitalization in the intensive care unit
Measured: Through study completion, an average of 1 year
Duration of mechanical ventilation
Measured: Through study completion, an average of 1 year
SOFA Score
Sequential Organ Failure Min Score 0-Max score 24 Higher scores mean a worse outcome
Measured: At Day 1,3,5,7,10 after randomization
Heart rate
Measured: At Day 1,3,5,7,10 after randomization
Respiratory Rate
Measured: At Day 1,3,5,7,10 after randomization
Spo2/FiO2 and ROX ratio
Measured: At Day 1,3,5,7,10 after randomization
CRP level
Measured: At Day 1,3,5,7,10 after randomization
LDH level
Measured: At Day 1,3,5,7,10 after randomization
D-Dimere level
Measured: At Day 1,3,5,7,10 after randomization
Platelet count
Measured: At Day 1,3,5,7,10 after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2021
- Study start10 Apr 2021 (estimated)
- Primary completion1 Nov 2021 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Viral PneumoniaStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ciusss de L'Est de l'Île de Montréal
- Sponsor type
- University, hospital or other
- Collaborators
- Covid-19 Early Treatment Fund
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04820751
- Sponsor's protocol ID
- 25584
- Status last verified
- Mar 2021
- First submitted
- 25 Mar 2021
- Last updated
- 2 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cyproheptadine in Severe COVID-19 : A Unblinded Randomized Trial
- ClinicalTrials.gov ID
- NCT04820751
- Acronym / sponsor ID
- 25584
- Conditions
- Viral Pneumonia, Serotonin Syndrome, Platelet Dysfunction
- Keywords
- Covid 19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Ciusss de L'Est de l'Île de MontréalUniversity, hospital or other
- Collaborators
- Covid-19 Early Treatment Fund
- Study start
- 10 Apr 2021 (estimated)
- Primary completion
- 1 Nov 2021 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 29 Mar 2021 (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.
This randomized controled open label clinical trial is to evaluate the effect of Cyproheptadine on the clinical course of patients presenting a severe SARS-COV 2 pneumonia.
Detailed description
Observational and biochemical studies have identified an interesting pathway in the pathophysiology of certain clinical-biological characteristics of COVID-19, linked to an excess of serotonin. We hypothesize that the antagonism of the action of serotonin could improve the clinical course of patients most severely affected by COVID-19.
One such antagonist of serotonin with a long track record of safety and tolerability is cyproheptadine. Cyproheptadine acts as an antagonist of 5-hydroxytryptamine (5HT=serotonin) receptor subtype 2 as well as histamine-1 receptor. Many of the potent effects of serotonin on lung vascular tone, respiratory rate, and systemic vascular beds are mediated by 5-HT receptor subtype 2.
Investigators will randomize approximately 200 participants, aged 18 and older, who have tested positive for COVID-19 and who will be hospitalized at Santa Cabrini Hospital in Montreal, Quebec, Canada, presenting a severe form of covid-pneumonia-19 requiring supplemental oxygen.
Study eligibility of all participants will be assessed first. Once a participant is confirmed eligible and consented, they will participate in the study.
Participants will be randomly assigned (1: 1) to either take cyproheptadine 8 mg by mouth three times a day for 5 days and receive standard care or receive standard care alone.
The dose will be adjusted according to the glomerular filtration rate.
On D1, D3, D5, D7 and D10 since randomization, participant's vital signs (including SpO2, respiratory rate, FiO2 or oxygen flow, heart rate, blood pressure and temperature), blood creatinine, bilirubin, CRP, LDH, Dimers and platelets the count will be evaluated. Any adverse event will be assessed daily and documented.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyproheptadine and standard care | Experimental | Drug: Cyproheptadine Hydrochloride 4 MGStart Cyproheptadine 8mg three times a day during 5 days. Dose will be reduced to 4mg three times a day if GFR inferior to 30ml/min/1.73m² Standard management of COVID-19 infection according to current international guidelines |
| Standard care | No intervention | –Standard management of COVID-19 infection according to current international guidelines |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and women age 18 or older
- Hospitalized and requiring medical care for COVID-19
- Presenting respiratory failure cause by COVID 19 requiring oxygen and/or mechanical ventilation support
- With radiographic evidence of pulmonary infiltrate
- Able to give informed consent or, if unable to do so regarding the medical condition, having relatives able of consenting for the patient
Key exclusion criteria (5 listed)
- Pregnancy
- Patients with pre-existing terminal condition with life expectancy < 6 months
- Patients with pre-existing severe lung disease requiring home O2
- History of seizure disorder
- History of adverse reaction to antihistamines or to Cyproheptadine
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 |
|---|---|---|
| Cyproheptadine Hydrochloride 4 MGAlso: Standard CareCyproheptadine associated to standard care | Drug | Cyproheptadine and standard care |
Primary outcome
Length of hospitalization
Time frame: Through study completion, an average of 1 year
Need mechanical ventilation (Non invasive or Invasive)
Time frame: Through study completion, an average of 1 year
11 secondary outcomes
Death
Time frame: Day 28
Length of hospitalization in the intensive care unit
Time frame: Through study completion, an average of 1 year
Duration of mechanical ventilation
Time frame: Through study completion, an average of 1 year
SOFA Score
Time frame: At Day 1,3,5,7,10 after randomization
Heart rate
Time frame: At Day 1,3,5,7,10 after randomization
Respiratory Rate
Time frame: At Day 1,3,5,7,10 after randomization
Spo2/FiO2 and ROX ratio
Time frame: At Day 1,3,5,7,10 after randomization
CRP level
Time frame: At Day 1,3,5,7,10 after randomization
LDH level
Time frame: At Day 1,3,5,7,10 after randomization
D-Dimere level
Time frame: At Day 1,3,5,7,10 after randomization
Platelet count
Time frame: At Day 1,3,5,7,10 after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2021.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyproheptadine Hydrochloride 4 MG in people with Viral Pneumonia and Serotonin Syndrome, run by Ciusss de L'Est de l'Île de Montréal.
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 5 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 2 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Philippe Rola, MD (514 252-6000, philippe.rola@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Length of hospitalization (time frame: Through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Apr 2021.