| CTRI Number |
CTRI/2021/08/035822 [Registered on: 19/08/2021] Trial Registered Prospectively |
| Last Modified On: |
16/08/2021 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Assessment of doubling dose of dexamethasone in progressively worsening severe COVID-19 pneumonia - a randomized controlled trial |
|
Scientific Title of Study
|
Assessment of doubling dose of dexamethasone in progressively worsening severe COVID-19 pneumonia not responding to standard dose - an open-label pragmatic randomized controlled trial |
| Trial Acronym |
ADDED |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| nil |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Animesh Ray |
| Designation |
Assistant Professor |
| Affiliation |
All India Institute of Medical Sciences, New Delhi |
| Address |
Room no. 3070A,Department of Medicine,
3rd floor teaching block,
All India Institute of Medical Sciences,
New Delhi-110029
South West
DELHI
110029
India |
| Phone |
01126593963 |
| Fax |
|
| Email |
doctoranimeshray@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Animesh Ray |
| Designation |
Assistant Professor |
| Affiliation |
All India Institute of Medical Sciences, New Delhi |
| Address |
Room no. 3070A,Department of Medicine,
3rd floor teaching block,
All India Institute of Medical Sciences,
New Delhi-110029
South West
DELHI
110029
India |
| Phone |
01126593963 |
| Fax |
|
| Email |
doctoranimeshray@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Satish Swain |
| Designation |
Senior resident, Infectious diseases |
| Affiliation |
All India Institute of Medical Sciences, New Delhi |
| Address |
Medicine office,Department of Medicine,
3rd floor teaching block,
All India Institute of Medical Sciences,
New Delhi-110029
South West
DELHI
110029
India |
| Phone |
|
| Fax |
|
| Email |
satishswain9@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute of Medical Sciences, New Delhi |
|
|
Primary Sponsor
|
| Name |
Animesh Ray |
| Address |
Room no. 3070A,Department of Medicine,
3rd floor teaching block,
All India Institute of Medical Sciences,
New Delhi-110029 |
| Type of Sponsor |
Other [Self] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Animesh Ray |
Jai Prakash Narayan Apex Trauma Centre, AIIMS , New Delhi |
Room no. 3070A,Department of Medicine,
3rd floor teaching block,
All India Institute of Medical Sciences,
New Delhi-110029
South West
DELHI |
01126593963
doctoranimeshray@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee, AIIMS, New Delhi |
Approved |
|
|
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 |
Dexamethasone 12 mg |
Dexamethasone 12 mg, once daily, through intravenous or oral route, for 10 days or till day of discharge, whichever is earlier. |
| Comparator Agent |
Dexamethasone 6 mg |
Dexamethasone 6 mg, once daily, through intravenous or oral route, for 10 days or till discharge, whichever is earlier |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
Patients aged at least 18 years, hospitalised, confirmed SARS-CoV-2 infection by nucleic acid based testing (RT-PCR, CB-NAAT, or TrueNAT) or antigen testing, Severe COVID-19 pneumonia (SpO2 <94%; PaO2/FiO2 <300 mm Hg or respiratory rate(RR) >30 breaths/min) with lack of response to Dexamethasone 6 mg after 48 hours [defined as similar or worsening oxygen requirement (margin of error is 5% Fio2 for high flow nasal cannula, 2 L/min for NRBM, and 1 L/min for low flow oxygen devices)]
|
|
| ExclusionCriteria |
| Details |
Patient already on corticosteroid therapy for an unrelated indication; Patient with impending death or respiratory failure necessitating ICU care within 24 hours including inability to maintain SpO2 ≥90% despite HFNC with flow 60 L/min and FiO2 1.0 or ,if available, NIV with PEEP of upto 8 cm H2O and FiO2 1.0; Patients who have received ≥2 day of steroids outside hospital care or within the hospital outside of wards that are involved in the study. These doses must be no greater than 12 mg dexamethasone or 64 mg methylprednisolone cumulatively; Patients with a known contraindication to corticosteroids including untreated bacterial sepsis, diabetic keto-acidosis, and invasive fungal infections such as mucormycosis; medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial; Pregnancy; Recruitment in another therapeutic trial; Use of immunosuppressive drugs, cytotoxic chemotherapy in the past 21 days; Neutropenia due to hematological or solid malignancies with bone marrow invasion; Refusal of consent.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
Supplemental oxygen-free days at day 28 from hospitalization
Proportion of patients requiring non-invasive ventilation by NIV mask or invasive mechanical ventilation |
Day 28 from hospitalisation, during hospital course |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| In-hospital mortality |
At death/discharge |
| All cause mortality at day 28 from hospitalization |
Day 28 from hospitalisation |
| Hospital length of stay |
At death/discharge |
| Number of days to requirement for NIV or invasive mechanical ventilation |
During Hospital course |
| Proportion of patients requiring antimicrobial therapy for suspected hospital acquired infection (bacterial or fungal) |
During hospital course |
| Clinical status after 5 as well as 10 days after hospitalization with 9-point WHO ordinal scale |
Day 5 and 10 after hospitalisation |
| Severity of steroid induced hyperglycemia including average daily glucose measurements and average daily insulin administered per kilogram body weight from day 1-5 after randomization |
Day 1-5 after randomisation during hospital course |
|
|
Target Sample Size
|
Total Sample Size="120"
Sample Size from India="120"
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
|
Phase 3 |
|
Date of First Enrollment (India)
|
01/09/2021 |
| 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="0"
Months="6"
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 - All of the individual participant data collected during the trial, after de-identification.
- What additional supporting information will be shared?
Response - Study Protocol
Response - Statistical Analysis Plan
Response - Analytic Code
- 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 - Any purpose.
- By what mechanism will data be made available?
Response (Others) - Proposals should be directed to doctoranimeshray@gmail.com.
- For how long will this data be available start date provided 01-01-2022 and end date provided 31-12-2022?
Response - Immediately following publication. No end date.
- Any URL or additional information regarding plan/policy for sharing IPD?
Additional Information - NIL
|
|
Brief Summary
|
This is a single centre, open label, parallel-arm, randomized trial to assess whether dexamethasone 6mg alone versus escalation of dexamethasone to 12mg in patients with progressive severe COVID 19 illness would be effective in improving the outcomes of patients with severe COVID 19 infection. This study would be conducted in the Trauma center (TC), AIIMS, which is a dedicated COVID center. The diagnosed cases of COVID-19 pneumonia with hypoxemia who would fulfil the criteria for severe COVID-19 as per the CDC definition (SpO2 <94% on room air, a ratio of arterial partial pressure of oxygen to FiO2 (PaO2/FiO2) <300 mm Hg or respiratory rate(RR) >30 breaths/min) would be included. This definition encompasses both moderate (SpO2 <94%) and severe (SpO2 <90%) COVID-19 pneumonia as per our institute protocol. All eligible patients would be recruited and initiated on standard care (remdesivir 200mg i.v. loading dose, followed by 100 mg i.v. once daily for 4 days, and anticoagulation-LMWH such as enoxaparin 0.1 mg/kg upto 40 mg according to the institute COVID 19 treatment protocol). Patients whose respiratory parameters worsen or remain plateau on standard of care beyond 24 hours upto 5 days of admission would be randomized to one of two arms (A) and (B). Arm A: Dose of steroids increased (12 mg i.v. once daily, i.v. or oral) Arm B: Dose of steroids unchanged (6 mg i.v. once daily or oral
The duration of the steroid in either arm would be for a total period of 10 days or till the patient’s discharge from the hospital, whichever is earlier. The objective of the study is to evaluate the outcome of doubling the dose of steroid in patients with severe covid 19 pneumonia, those who worsen or remain plateau within 5 days of hospitalization compared to standard of care. |