Cyproheptadine in Severe COVID-19 : A Unblinded Randomized Trial

March 31, 2021 updated by: Ciusss de L'Est de l'Île de Montréal
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cyproheptadine and standard care

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
Drug: Cyproheptadine Hydrochloride 4 MG
Cyproheptadine associated to standard care
Other Names:
  • Standard Care
No Intervention: Standard care
Standard management of COVID-19 infection according to current international guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Length of hospitalization
Time Frame: Through study completion, an average of 1 year
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
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death
Time Frame: Day 28
Day 28
Length of hospitalization in the intensive care unit
Time Frame: Through study completion, an average of 1 year
Through study completion, an average of 1 year
Duration of mechanical ventilation
Time Frame: Through study completion, an average of 1 year
Through study completion, an average of 1 year
SOFA Score
Time Frame: At Day 1,3,5,7,10 after randomization
Sequential Organ Failure Min Score 0-Max score 24 Higher scores mean a worse outcome
At Day 1,3,5,7,10 after randomization
Heart rate
Time Frame: At Day 1,3,5,7,10 after randomization
At Day 1,3,5,7,10 after randomization
Respiratory Rate
Time Frame: At Day 1,3,5,7,10 after randomization
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
At Day 1,3,5,7,10 after randomization
CRP level
Time Frame: At Day 1,3,5,7,10 after randomization
At Day 1,3,5,7,10 after randomization
LDH level
Time Frame: At Day 1,3,5,7,10 after randomization
At Day 1,3,5,7,10 after randomization
D-Dimere level
Time Frame: At Day 1,3,5,7,10 after randomization
At Day 1,3,5,7,10 after randomization
Platelet count
Time Frame: At Day 1,3,5,7,10 after randomization
At Day 1,3,5,7,10 after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ciusss de L'Est de l'Île de Montréal

Collaborators

Covid-19 Early Treatment Fund

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

April 10, 2021

Primary Completion (Anticipated)

November 1, 2021

Study Completion (Anticipated)

January 1, 2022

Study Registration Dates

First Submitted

March 25, 2021

First Submitted That Met QC Criteria

March 26, 2021

First Posted (Actual)

March 29, 2021

Study Record Updates

Last Update Posted (Actual)

April 2, 2021

Last Update Submitted That Met QC Criteria

March 31, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 25584

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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