Phase II RCT to Assess Efficacy of Intravenous Administration of Oxytocin in Patients Affected by COVID-19

NCT04386447 | Withdrawn Phase 2 DMC

• 1 other identifier: OsCOVID19
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 3

Brief Summary

Introduction There are currently no treatments with demonstrated efficacy for COVID-19 infection. Epidemiological evidence points to the existence of intrinsic protection factors which make young persons and women more resistant to the infection, whereas older patients with multiple illnesses, above all with heart disease, are at greatest risk. This trial proposes treatment initiated in the early stages of the disease, when clinical worsening is most likely, with intravenous Oxytocin (OT), an endogenous hormone currently safely used in clinical practice. The selection of this molecule is based on numerous experimental and clinical observations, which show its activity in modulating resistance to pathogens, in mitigating overall cardiovascular risk, and in acting on the production of Nitric Oxide (ON) in the lungs, which is emerging as a key therapeutic factor for the improvement of respiratory function in patients with SARS-COVID 19. Finally, OT is physiologically produced by the human body, especially in the female sex and in the age ranges that coincide with most resistant patients. In routine clinical practice, OT exhibits an excellent therapeutic index, in absence of significant adverse effects. Primary aim To assess the effects of Oxytocin in addition to standard therapy, with respect to Standard of Care (SoC), in reducing the number of patients who enter a critical stage Secondary aim To describe:

• Mortality 28 days after randomization
• Time to mechanical ventilation during the study
• Duration of dependency on oxygen supply
• Length of stay
• Temporal trend of clinical improvement (7-category ordinal scale)
• Safety analysis

Conditions

Covid-19; Corona Virus Infection; SARS-CoV 2

Keywords

Covid-19; Oxytocin; Corona Virus Infection

Outcome Measures

Primary Outcomes (1)

• Proportion of cases who during 14 exhibit one of the following conditions

  Proportion of cases who during 14 days exhibit one of the following conditions (the most severe): * respiratory failure that requires mechanical ventilation * organ failure that requires intensive care monitoring and treatment * death

  14 days

Secondary Outcomes (1)

• Mortality 28 days after randomization

  28 days

Study Arms (3)

Oxytocin 40 UI + SOC

EXPERIMENTAL

In addition to standard treatment, patients in the experimental arm will receive intravenous OT with dilution of 40 UI OT in 500cc physiological solution NaCl 9%. OT will be administered with continuous pump infusion with 62,5 ml/h. The clinician will have the option to decrease infusion speed based on significant variations in arterial pressure, otherwise, the total 25 UI or 40 UI amount will be infused in 8 hours. Treatment duration will be 10 days

Drug: Oxytocin

Oxytocin 25 UI + SOC

EXPERIMENTAL

In addition to standard treatment, patients in the experimental arm will receive intravenous OT with dilution of 25 UI OT in 500cc physiological solution NaCl 9%. OT will be administered with continuous pump infusion with 62,5 ml/h. The clinician will have the option to decrease infusion speed based on significant variations in arterial pressure, otherwise, the total 25 UI or 40 UI amount will be infused in 8 hours. Treatment duration will be 10 days

Drug: Oxytocin

Standard of Care

OTHER

Standard of Care (SoC). Standard of Care will comply with the indications of the Emilia-Romagna Region for the treatment of covid-19, and will include the following: * Oxygen supply or non-invasive ventilation to target peripheral blood saturation \> 94% * Hydroxychloroquine 200mg b.i.d w/o an initial 1-2 days loading dose of 400 mg bid for 1-2 days (the dose may be reduced in patients with advanced CKD according to local protocols) or remdesivir 200 mg in.v on day 1, followed by a 100 mg q.d. * Antiretroviral therapy (usually for 5 days) with lopinavir / ritonavir or darunavir / cobicistat is permitted * Azithromycin 500 mg q.d., usually for 5 days, is permitted in patients with suspected bacterial superinfection, paying particular attention to safety, considering reports of risk of adverse events in association with hydroxychloroquine * Prophylaxis for deep vein thrombosis * Steroids are not routinely recommended but may be considered in selected patients.

Drug: Standard of Care

Interventions

Oxytocin DRUG

In addition to standard treatment, patients in the experimental arm will receive intravenous OT with dilution of 25 UI or 40 UI OT in 500cc physiological solution NaCl 9%. OT will be administered with continuous pump infusion with 62,5 ml/h. The clinician will have the option to decrease infusion speed based on significant variations in arterial pressure, otherwise, the total 25 UI or 40 UI amount will be infused in 8 hours. Treatment duration will be 10 days

Also known as: Oxytocin OT

Oxytocin 25 UI + SOC; Oxytocin 40 UI + SOC

Standard of Care DRUG

Standard of Care (SoC). Standard of Care will comply with the indications of the Emilia-Romagna Region for the treatment of covid-19, and will include the following: * Oxygen supply or non-invasive ventilation to target peripheral blood saturation \> 94% * Hydroxychloroquine 200mg b.i.d w/o an initial 1-2 days loading dose of 400 mg bid for 1-2 days (the dose may be reduced in patients with advanced CKD according to local protocols) or remdesivir 200 mg in.v on day 1, followed by a 100 mg q.d. * Antiretroviral therapy (usually for 5 days) with lopinavir / ritonavir or darunavir / cobicistat is permitted * Azithromycin 500 mg q.d., usually for 5 days, is permitted in patients with suspected bacterial superinfection, paying particular attention to safety, considering reports of risk of adverse events in association with hydroxychloroquine * Prophylaxis for deep vein thrombosis * Steroids are not routinely recommended but may be considered in selected patients.

Also known as: SOC

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Diagnosis of pneumonia caused by COVID-19
• Respiratory and/or systemic symptoms and initial mild respiratory failure and with objective signs of lung involvement
• Respiratory frequency ≥25/min, blood oxygen saturation (SaO2) \< 95% in A-A, PaO2/FiO2 ratio \< 300
• Hospital admission since less than 48 hours
• Signature of informed consent for study participation

You may not qualify if:

• MEWS score \> 4
• Severe multiple organ failure
• Recent cardiomyopathy, unstable angina, acute myocardial infarction
• Severe kidney failure with glomerular filtration rate less than 30 ml/min or renal replacement therapy or peritoneal dialysis
• History of diabetes insipidus or severe hyponatremia (\<128 mEq/L) or hypernatremia (\>155 mEq/L)
• QT interval which in the opinion of the patient's treating physician contraindicates therapy with OT
• State of shock
• Women who are pregnant or nursing
• Known intolerance or hypersensitivity to the drug or its excipients
• Treatment with antirejection agents
• Individuals with severe liver failure
• Patients enrolled in other clinical trials

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Parma: lead
• University of Parma: collaborator

Study Sites (3)

CNRS

Lyon, France

Location

Azienda Ospedaliero Universitaria di Parma

Parma, PR, 43100, Italy

Location

Ospedale San Francesco

Nuoro, Italy

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

Oxytocin; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Tiziana Meschi, MD,PhD

  Azienda Ospedaliero-Universitaria di Parma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Geriatric Rehabilitation Medical Department

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 13, 2020
• Study Start: September 1, 2020
• Primary Completion: October 31, 2020
• Study Completion: December 31, 2020
• Last Updated: January 14, 2021

Record last verified: 2021-01

Locations

FR (1); IT (2)