Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia (SCOPE)

• ClinicalTrials.gov Identifier: NCT04341675
• Recruitment Status: Unknown
• First Posted: April 10, 2020
• Last Update Posted: May 20, 2020
• Sponsor: University of Cincinnati
• Information provided by (Responsible Party): Nishant Gupta, MD, MS, University of Cincinnati

Study Description

Brief Summary:

The main objective of our study is to determine if treatment with sirolimus can improve clinical outcomes in hospitalized patients with COVID-19. The investigators will employ a randomized, double blind, placebo-controlled study design. 30 subjects will be randomized in a 2:1 fashion to receive sirolimus or placebo. Sirolimus will be given as a 6mg oral loading dose on day 1 followed by 2mg daily for a maximum treatment duration of 14 days or until hospital discharge, whichever happens sooner. Chart reviews will be conducted daily to determine changes in clinical status, concomitant medications and laboratory parameters. Study specific biomarkers will be measured at baseline and then at days 3, 7 and 14.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Sirolimus; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randmized, double blind, placebo controlled
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia (The SCOPE Trial)
• Actual Study Start Date: April 24, 2020
• Estimated Primary Completion Date: July 2020
• Estimated Study Completion Date: September 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Sirolimus; Sirolimus 6mg on day 1 followed by 2mg daily for the next 13 days or until hospital discharge, whatever happens sooner.	Drug: Sirolimus; Sirolimus 6mg daily on Day 1 followed by 2mg daily for the next 13 days for a total treatment duration of 14 days or hospital discharge, whatever happens sooner.; Other Name: Rapamycin
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo; Matching placebo; Other Name: placebo capsules

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients who are alive and free from advanced respiratory support measures at day 28. [ Time Frame: 28 days ]

   Death or progression to respiratory failure requiring advanced support measures, either due to inadequate ventilation (non-invasive or invasive mechanical ventilation) or inadequate oxygenation (CPAP* or high flow supplemental oxygen at rates ≥ 15 liters/minute), in patients given sirolimus compared to the placebo group.

   * CPAP use for known obstructive sleep apnea will not be considered as disease progression.

Secondary Outcome Measures :

1. Proportion of patients who require escalation in care [ Time Frame: 14 days ]
   Progression to a higher level of care, e.g. ICU
2. Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count) [ Time Frame: 14 days ]
   Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count)
3. Proportion of patients surviving to hospital discharge [ Time Frame: days ]
   Survival to hospital discharge
4. Drug safety profile [ Time Frame: 14 days ]
   Incidence and type of adverse events
5. Duration of advanced respiratory support [ Time Frame: days ]
   Number of days spent on advanced respiratory support measures
6. Duration of hospital stay [ Time Frame: days ]
   Length of hospitalization (in patients who survive to discharge)
7. Time from treatment initiation to death [ Time Frame: days ]
   Number of days between study initiation and death (in the subset of patients who die during the hospitalization)
8. Time to resolution of fever [ Time Frame: 14 days ]
   Time (in days) to resolution of fever
9. Proportion of patients who require initiation of off-label therapies [ Time Frame: 14 days ]
   Patients needing off-label treatments such as Anti-IL-6 inhibitors at the discretion of primary clinicians

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Subjects enrolled in the trial must meet all of the following criteria.

• Confirmed COVID-19 pneumonia
• Hypoxia as defined by room air oxygen saturation less than 92% or supplemental oxygen requirement
• Presence of at least one additional biomarker that has been shown to predict poor prognosis: a) serum ferritin ≥500ug/l, b) LDH ≥250U/L, c) d-dimer ≥1ug/L, or d) lymphopenia as defined by absolute lymphocyte count <1,000/uL
• Age ≥ 18 years
• Completed informed consent

Exclusion Criteria:

Subjects who meet ANY of the following criteria are not eligible for enrollment as study participants:

• Known allergy or hypersensitivity to sirolimus
• Inability or refusal to provide informed consent
• Advanced respiratory support (high flow oxygen ≥ 15 L/min, CPAP, non-invasive or invasive mechanical ventilation)
• Active enrollment in other interventional clinical drug trials. Co-enrollment in observational studies and biorepositories is allowed.
• Pregnant women
• Breast feeding
• On chronic immunosuppression for other medical conditions such as rheumatological disorders, inflammatory bowel disease, or in patients with organ transplants. A list of these medications is provided in Section 12.3.4

• Any clinically significant medical disease which in the opinion of the investigator precludes the patient from enrolling in the trial, including (but not limited to):

  • History of liver cirrhosis
  • End stage renal disease or need for renal replacement therapy
  • Decompensated heart failure
  • Known active tuberculosis or history of incompletely treated tuberculosis
  • Uncontrolled systemic bacterial or fungal infections
  • Active viral infection other than COVID-19

Contacts and Locations

Contacts

Contact: Nishant Gupta, MD; 5135584831; guptans@ucmail.uc.edu

Locations

United States, Illinois

Loyola University Medical Center; Active, not recruiting

Chicago, Illinois, United States, 60153

United States, Ohio

University of Cincinnati; Recruiting

Cincinnati, Ohio, United States, 45267

Contact: Davis Alexandria 513-558-2187 davis5ax@ucmail.uc.edu

Principal Investigator: Nishant Gupta, MD

Sponsors and Collaborators

University of Cincinnati

Investigators

• Principal Investigator: Nishant Gupta, MD; University of Cincinnati

More Information

• Responsible Party: Nishant Gupta, MD, MS, Adjunct Associate Professor, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT04341675
• Other Study ID Numbers: 2020-0337
• First Posted: April 10, 2020
• Last Update Posted: May 20, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: De-identified aggregate data will be made available to other researchers on a case-by-case basis.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

COVID-19; Pneumonia; Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Sirolimus; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs