Clinical trial NCT04979221: Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients With COVID-19
Official title: Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients With COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19 Pneumonia
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2021-07-28
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized controled open label clinical trial conducted in patients with hypoxemic respiratory failure admitted to the ICU and requiring ventilatory support (invasive or non-invasive) is to evaluate whether treatment with cyproheptadine, a serotonin receptor antagonist, compared to usual care, increases the number of ventilator-free days.

Detailed description: Some studies have shown increased platelet activation and reactivity in patients with COVID-19. This platelet activation is associated with serotonin release. Some characteristics observed during the evolution of COVID-19 may be associated with these increased levels of serotonin. In this scenario, the antagonism of the action of serotonin could improve the clinical course of patients affected by COVID-19. Cyprohepatdine is an anti-serotonergic antihistamine drug with a long track record of safety and tolerability.

Investigators will randomize 274 patients who have tested positive for COVID-19 and who will be admitted to the ICU requiring ventilatory support (invasive or non-invasive).

Patients will be randomized to a 1:1 ratio for receiving usual care + cyproheptadine (8mg three times a day for 10 days) or usual care.

Patients will be followed until discharge to determine length of stay in the ICU and hospital, mortality in the ICU and hospital and days free from ventilatory support during the first 28 days.

Eligibility criteria: Inclusion Criteria:

* Positive PCR for SARS-Cov-2
* ICU admission \< 48 hours
* Age 18 years or older
* Need for invasive or non-invasive ventilatory support (non-invasive ventilation or high-flow nasal cannula) \< 48 hours

Exclusion Criteria:

* Pregnancy or breastfeeding
* Refusal to sign the informed consent form
* Expected death in the next 24 hours
* Patients taking routinely SSRI or monoamine oxidase inhibitor therapy
* Impossibility of using the enteral route
* History of seizure disorder
* History of adverse reaction to antihistamines or to cyproheptadine
* Readmission to the ICU

Primary outcomes:
measure: Ventilatory support
timeFrame: Day 28
Secondary outcomes:
measure: Mechanical ventilation
timeFrame: Through study completion, an average of 6 months
measure: Mortality during 28 days
timeFrame: Day 28
measure: ICU Mortality
timeFrame: Through study completion, an average of 6 months
measure: Hospital Mortality
timeFrame: Through study completion, an average of 6 months
measure: Length of stay in the intensive care unit
timeFrame: Through study completion, an average of 6 months
measure: Length of stay in the hospital
timeFrame: Through study completion, an average of 6 months
measure: Renal replacement therapy
timeFrame: Day 28
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clínica de Porto Alegre
state: Rio Grande Do Sul
Study officials:
affiliation: Hospital de Clínicas de Porto Alegre
name: Marcio M Boniatti, PhD
role: PRINCIPAL_INVESTIGATOR
References: