NCT04970719

The Efficacy of Baricitinib Plus Remdesivir Compared to Dexamethasone Plus Remdesivir in Hospitalised COVID-19 Patients With Diabetes Mellitus

Withdrawn Phase 3 Last updated 7 April 2024

What this trial tests

Phase 3 trial testing Baricitinib in COVID-19 Pneumonia. Withdrawn.

Timeline

10 July 2021

Primary endpoint
1 December 2021

1 December 2021

Quick facts

Lead sponsor	Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders
Phase	Phase 3
Status	Withdrawn
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Start date	10 July 2021
Primary completion	1 December 2021
Estimated completion	1 December 2021
Sites	7 locations across Bangladesh

Drugs / interventions tested

• Baricitinib (baricitinib) — full drug profile →
• Dexamethasone (dexamethasone) — full drug profile →
• Remdesivir (remdesivir) — full drug profile →

Conditions studied

• COVID-19 Pneumonia — all drugs for COVID-19 Pneumonia →

Sponsor

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

Who can join

18 and older, any sex, with COVID-19 Pneumonia. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Rescue treatment
  Time frame: Day 2 through Day 29
  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 tim

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.
   Drożdżal S, Rosik J, Lechowicz K, Machaj F, et al · · 2021 · cited 186× · PMID 34991982 · DOI 10.1016/j.drup.2021.100794
2. The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication.
   Ning Q, Wu D, Wang X, Xi D, et al · · 2022 · cited 64× · PMID 35197452 · DOI 10.1038/s41392-022-00907-1
3. Immunotherapy of COVID-19: Inside and Beyond IL-6 Signalling.
   Zizzo G, Tamburello A, Castelnovo L, Laria A, et al · · 2022 · cited 55× · PMID 35340805 · DOI 10.3389/fimmu.2022.795315
4. Acute Respiratory Distress Syndrome and COVID-19: A Literature Review.
   Hussain M, Khurram Syed S, Fatima M, Shaukat S, et al · · 2021 · cited 38× · PMID 34992415 · DOI 10.2147/jir.s334043
5. Janus kinase inhibitors for the treatment of COVID-19.
   Kramer A, Prinz C, Fichtner F, Fischer AL, et al · · 2022 · cited 34× · PMID 35695334 · DOI 10.1002/14651858.cd015209
6. An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19).
   Elahi R, Karami P, Heidary AH, Esmaeilzadeh A. · · 2022 · cited 33× · PMID 35074571 · DOI 10.1016/j.intimp.2022.108536
7. JAK inhibition as a new treatment strategy for patients with COVID-19.
   Huang J, Zhou C, Deng J, Zhou J. · · 2022 · cited 25× · PMID 35787993 · DOI 10.1016/j.bcp.2022.115162
8. Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review.
   Jain NK, Tailang M, Jain HK, Chandrasekaran B, et al · · 2023 · cited 24× · PMID 37021053 · DOI 10.3389/fphar.2023.1135145