| CTRI Number |
CTRI/2021/11/037866 [Registered on: 08/11/2021] Trial Registered Prospectively |
| Last Modified On: |
01/11/2021 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Baricitinib in hospitalized patients with COVID19 pneumonia: COVID-BAR Trial |
|
Scientific Title of Study
|
A multicenter, randomized, controlled, parallel-design trial evaluating Baricitinib in hospitalized patients with COVID19 pneumonia (COVID-BAR trial) |
| Trial Acronym |
COVID-BAR |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Ritin Mohindra |
| Designation |
Assistant Professor |
| Affiliation |
PGIMER, Chandigarh |
| Address |
Department of Internal Medicine, Nehru Hospital,
PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
|
| Fax |
|
| Email |
ritin.mohindra@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Nanda Gamad |
| Designation |
Assistant Professor |
| Affiliation |
PGIMER, Chandigarh |
| Address |
Department of Pharmacology, Research Block B, 4th floor,
PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
|
| Fax |
|
| Email |
nanda.gamad@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Nanda Gamad |
| Designation |
Assistant Professor |
| Affiliation |
PGIMER, Chandigarh |
| Address |
Department of Pharmacology, Research Block B, 4th floor,
PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
|
| Fax |
|
| Email |
nanda.gamad@gmail.com |
|
|
Source of Monetary or Material Support
|
| Post Graduate Institute of Medical Education and Research, Chandigarh |
|
|
Primary Sponsor
|
| Name |
PGIMER Chandigarh |
| Address |
PGIMER, Sector 12, Chandigarh |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sanjay DCruz |
Government Medical College and Hospital Sector 32 |
Department of Internal Medicine
GMCH-32
Chandigarh
CHANDIGARH |
9646121556
sanjaydcruz@gmch.gov.in |
| Dr Honney Sawhney |
Government Multi Specialty Hospital Sector 16 |
Department of Internal Medicine
GMSH-16
Chandigarh
CHANDIGARH |
9814742949
dr.honney_sawhney@yahoo.com |
| Dr Nanda Gamad |
PGIMER |
NHE, PGIMER
Chandigarh
CHANDIGARH |
8447483823
nanda.gamad@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| IEC GMCH32 |
Submittted/Under Review |
| IEC PGIMER |
Approved |
| IECGMSH16 |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Baricitinib |
4 mg OD for up to 14 days |
| Comparator Agent |
Standard of care |
with or without remdesivir, dexamethasone |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
18 years and above of either sex
Hospital admission within 10 days of RT-PCR positivity for COVID-19
SpO2 <94% at room air and require low flow oxygen support- through nasal canula,
venturi mask or non-rebreather mask
Normal procalcitonin- <0.4 ng/mL with no other evidence of any co- or secondary
bacterial, viral or fungal infection at the time of randomization
Considered to be an appropriate participant for intervention with an immunomodulatory
in the opinion of the investigator
Should be able to be maintained on venous thromboembolism prophylaxis or current
maintenance therapy during inpatient dosing period, according to institutional protocol |
|
| ExclusionCriteria |
| Details |
Those who are on high flow oxygen or noninvasive or invasive mechanical ventilation or ECMO at the time of randomization
Those on steroids for more than 10 days for any indication
Patient has received baricitinib or any other immunomodulatory agent such as tumor
necrosis factor [TNF] inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], T-cell or B-cell targeted therapies (rituximab), interferon, or Janus kinase (JAK) inhibitors for any indication within 4 weeks of the 1st dose of baricitinib
Patient has inability to supply direct informed consent or if it was not possible to obtain from Next of Kin or Independent Healthcare Provider on behalf of patient
Contraindications to study drugs, including history of hypersensitivity to the active substances or any of the excipients
Suspected or known active infections including but not limited to tuberculosis, hepatitis B or C (no blood screening required), herpes zoster or HIV.
Current or past (within 3 months) participation in any interventional clinical trial including COVID-19-related disease trials (observational studies allowed)
Patient moribund at presentation or screening or expected survival is <24h
Pregnant or lactating women at screening (or unwillingness to adhere to pregnancy
advice in protocol)
Either alanine transaminase or aspartate transaminase (ALT or AST) > 5 times the upper
limit of normal (ULN)
Stage 4 severe chronic kidney disease or requiring dialysis (i.e. Cockcroft Gault estimated
creatinine clearance < 30 ml /min)
Currently receiving or ever received hyperimmune globulin, convalescent plasma or
intravenous immunoglobulin [IVIg]) for COVID-19
Patient has received neutralizing antibodies, such as bamlanivimab-etesevimab,
casirivimab-imdevimab and sotrovimab for COVID-19.
Patient has history of venous thromboembolism (VTE) (deep vein thrombosis [DVT]
and/or pulmonary embolism [PE]) within 12 weeks prior to randomization or has a history
of recurrent (>1) VTE
Current diagnosis of active malignancy that, in the opinion of the investigator, could
constitute a risk when taking investigational product
Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the patient ineligible for inclusion because of a safety concern |
|
|
Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Proportion of death or respiratory failure |
Day 28 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Proportion of death |
Day 14 and Day 28 |
| Proportion of respiratory failure |
Day 14 and Day 28 |
| Change in clinical status as assessed on NIAID 8-point ordinal scale compared to baseline |
Day 28 |
| Proportion of participants who require noninvasive ventilation |
Day 14 and Day 28 |
| Proportion of participants who require invasive ventilation |
Day 14 and Day 28 |
| Proportion of participants who require oxygen |
Day 14 and Day 28 |
| Proportion of participants with adverse events of special interest in each treatment arm |
Day 14, Day 28 and Day 180 |
| Incidence of laboratory confirmed secondary bacterial infections |
Day 28 |
| Incidence of laboratory confirmed secondary fungal infections |
Day 28 and Day 180 |
| Incidence of thrombotic events |
Day 28 |
| Time to SpO2 94% on room air |
Day 180 |
| Duration of oxygen therapy |
Day 180 |
| Duration of noninvasive ventilation |
Day 180 |
| Duration of invasive ventilation |
Day 180 |
| Duration of hospitalization |
Day 180 |
| Duration of ICU days |
Day 180 |
Percentage of Participants with a Change in Oxygen Saturation from 94% to ≥94% from
Baseline |
Day 28 |
| Time to clinical improvement |
Day 180 |
|
|
Target Sample Size
|
Total Sample Size="260"
Sample Size from India="260"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
15/11/2021 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
Nil |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
- What data in particular will be shared?
Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
- What additional supporting information will be shared?
Response - Clinical Study Report
- Who will be able to view these files?
Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
- For what types of analyses will this data be available?
Response - To achieve aims in the approved proposal.
- By what mechanism will data be made available?
Response - Proposals should be directed to [nanda.gamad@gmail.com].
- For how long will this data be available start date provided 01-01-2025 and end date provided 01-01-2030?
Response - Beginning 3 months and ending 5 years following article publication.
- Any URL or additional information regarding plan/policy for sharing IPD?
Additional Information - NIL
|
|
Brief Summary
|
Baricitinib is a selective reversible inhibitor of Janus kinases (JAK),
approved for rheumatoid arthritis and recently received emergency use
authorisation (EUA) for COVID19. The progression of COVID19 from
moderate to severe disease is characterized by striking elevation of IL-6
and other inflammatory markers. IL-6 signals via JAK1/2 receptors and
activates the intracellular STAT3 in T cells. Baricitinib potently inhibits this
pathway and also blocks non-IL-6 pathways through TYK2/JAK1 that signal
various other cytokines. It is also known to decrease viral entry into the
target cells mediated by ACE2 receptor. In an unpublished report (COV-
BARRIER trial), 1525 hospitalized adults with COVID-19 who were on high
or low flow oxygen, but did not receive invasive mechanical ventilation,
baricitinib was added to standard of care including steroids and remdesivir.
The results showed non-significant difference in the primary endpoint
which was a composite of those who will progress to receiving high-flow
oxygen, non-invasive and invasive ventilation and death at 28 days.
However, there was a significant reduction in 28-day mortality. In the
previously published landmark Adaptive COVID-19 Treatment Trial 2 (ACTT-
2), baricitinib plus remdesivir reduced time to recovery compared with
placebo plus remdesivir. On the contrary, 29-day mortality was not
statistically significant with the addition of baricitinib to remdesivir. Two
observational studies provide data on low dose and high dose baricitinib at
different time durations (2 mg and 8 mg respectively for 5 to 10 days and
14 days respectively). The United States Food and Drug Administration (US-
FDA) gave EUA to baricitinib in addition to remdesivir for COVID19 at the
dose of 1 mg or 2 mg in steroid naïve patients while National Institute of
Health (NIH) recommends use of baricitinib in COVID19 patients with
pneumonia for up to 14 days or until hospital discharge whichever is
earlier. Although Drug Controller General of India (DCGI) also gave EUA for
its use, it is not clear on the dose, duration and its administration with
current standard of care i.e, steroids. Hence, we decided to conduct a trial
evaluating the drug with current standard of care including remdesivir and
steroids and enrich data from India.
|