Baricitinib in Hospitalized Covid-19 Patients With Diabetes Mellitus

NCT04970719 | Withdrawn Phase 3

• 1 other identifier: BADAS-ERC/EC/21/00311
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 7

Brief Summary

To date, some of the most promising drugs used in the treatment of COVID pneumonia are systemic corticosteroids, remdesivir and baricitinib. Dexamethasone has been found efficacious in reducing mortality in patients requiring supplemental oxygen and mechanical ventilation. There is a trend towards reduced mortality in patients who receive remdesivir and dexamethasone combination, supporting the hypothesis that an antiviral drug combined with an anti-inflammatory agent improve outcomes in COVID-19. Baricitinib plus remdesivir is superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with COVID-19, notably among those receiving high-flow oxygen non-invasive ventilation. Diabetes mellitus increases the risk for COVID-19 morbidity and mortality. Patients with diabetes have coexisting morbidities and already immune-compromised. Steroids cause further immunosuppression and may contribute to uncontrolled blood glucose in this group of patients, resulting in worse outcomes. Baricitinib can be an alternative to corticosteroids in diabetic patients. This open-label multi-centre non-inferiority randomized controlled trial will be conducted in seven hospitals in Bangladesh. The primary objective is to evaluate the clinical efficacy of baricitinib plus remdesivir compared to dexamethasone plus remdesivir in hospitalized COVID-19 patients with diabetes mellitus, as assessed by the proportion of patients, need "rescue treatment" between two groups by day 29. Hospitalized adult (≥18 years) diabetic patients with confirmed SARS-CoV-2 infection have ordinal scale category 5 will be included in the study. Subjects will be randomized in a 1:1 (by tossing a coin) ratio in two groups. The total sample size is 362. Group 1 subjects will receive 200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily dose of remdesivir while hospitalized for up to 5 days and 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to 14 days. Group 2 will receive the same dose of remdesivir plus 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to 10 days. Subjects will be assessed daily while hospitalized. Discharged subjects will be evaluated on days 15, 22 and 29 (in person; if not possible, over the telephone). Assessment will be done clinically using an 8-point Ordinal Scale and National Early Warning Score.

Conditions

COVID-19 Pneumonia

Keywords

COVID-19; baricitinib; remdesivir; dexamethasone; diabetes mellitus; hospitalized

Outcome Measures

Primary Outcomes (1)

• Rescue treatment

  The proportion of subjects not requiring "rescue treatment". Rescue treatment will be given if there is a deterioration of the ordinal scale beyond category 5 (unable to maintain SpO2 ≥ 92% with 10 L/ min O2) at any time 24 hours after enrollment. 10 mg of dexamethasone will be administered on top of existing treatment in group 1 and escalate to in group 2 as an intravenous injection, 2 to 4 times daily for 3 to 5 days based on the patient's condition, then tapered. Patients who deteriorate beyond the ordinal scale category 5 within 24 hours of enrollment will be excluded from the study.

  Day 2 through Day 29

Secondary Outcomes (27)

• Death or invasive mechanical ventilation

  Day 2 through Day 29

• C-reactive protein (CRP)

  Day 1 through Day 29

• lactate dehydrogenase (LDH)

  Day 1 through Day 29

• Ferritin

  Day 1 through Day 29

• Creatinine

  Day 1 through Day 29

Study Arms (2)

Remdesivir plus Baricitinib

EXPERIMENTAL

200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 5-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course

Drug: Baricitinib; Drug: Remdesivir

Remdesivir plus Dexamethasone

ACTIVE COMPARATOR

200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 5 -day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.

Drug: Dexamethasone; Drug: Remdesivir

Interventions

Baricitinib DRUG

4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course

Also known as: Janus kinase inhibitors

Remdesivir plus Baricitinib

Dexamethasone DRUG

and 6 mg\* of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course

Also known as: Steroids

Remdesivir plus Dexamethasone

Remdesivir DRUG

200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 5-day total course

Also known as: Anti-viral

Remdesivir plus Baricitinib; Remdesivir plus Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Hospitalized diabetic adults with laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) in any respiratory specimen within 10 days prior to randomization or \*Hospitalized diabetic adults with typical features of COVID-19 for 10 days prior to randomization, not yet tested for SARS-CoV-2 infection by PCR in any respiratory specimen.
• RT-PCR for SARS-CoV-2 will be performed within 48 hours of enrollment and excluded from the study if found to be negative.
• point ordinal scale "category 5" patients, but O2 requirement not more than 10L / min.
• The subject provides informed consent before initiating any study procedures and understands and agrees to comply with planned study procedures

You may not qualify if:

• Patients with evidence (clinical, hematological, microbiological or imaging ) of sepsis or any acute/subacute coinfection at the time of enrollment.
• Patients who have already received any of the study drugs prior to randomization.
• Patients with severe renal and/or hepatic impairment (eGFR \<30 mL/min \[EPI-CKD formula\] or serum ALT more than 5 times normal upper limit, serum bilirubin \> 2 mg/dl).
• Patients with known COPD.
• Patients with absolute neutrophil count \<700 cells/microliter, 0.7 x 103/microliter.
• Patients with absolute lymphocyte count \<200 cells/microliter, 0.20 x 103/microliter.
• Patients who are allergic to any of the study drugs.
• Patients with chronic infections, such as tuberculosis (TB), HIV infection etc.
• Immunosuppressed patients, such as taking cytotoxic/immunomodulating drugs or systemic steroid.

Sponsors & Collaborators

• Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders: lead

Study Sites (7)

Debidwar Upazila Health Complex

Comilla, Bangladesh

Location

BIRDEM General Hospital

Dhaka, 1000, Bangladesh

Location

Mugda Medical College and Hospital

Dhaka, 2015, Bangladesh

Location

Kurmitola General Hospital

Dhaka, Bangladesh

Location

Kurigram Adhunik Sadar Hospital

Kurigrām, Bangladesh

Location

Rajshahi Medical College & Hospital

Rajshahi, Bangladesh

Location

Dedicated Corona Isolation Hospital (DCIH)

Rangpur City, Bangladesh

Location

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MeSH Terms

Conditions

COVID-19; Diabetes Mellitus

Interventions

baricitinib; Janus Kinase Inhibitors; Dexamethasone; Steroids; remdesivir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Wasim MM Haque, FCPS

  Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: July 21, 2021
• Study Start: July 10, 2021
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: April 9, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: relative to the time when summary data are published
• Access Criteria: all data will be available if required

Locations

BA (7)