Effect of the anti-inflammatory test drug anakinra in patients with coronavirus (COVID-19) requiring oxygen support

ISRCTN ISRCTN74727214
DOI https://doi.org/10.1186/ISRCTN74727214
Submission date
01/08/2020
Registration date
10/08/2020
Last edited
15/01/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study arms:
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.

Due to respiratory failure in patients with severe COVID-19, an inflammatory state may develop. It is hoped that the anti-inflammatory drug anakinra may be effective in neutralization of this inflammation and therefore may be lifesaving in selected patients with severe COVID-19 infection. This study aims to investigate whether anakinra may reduce the need for invasive mechanical ventilation and deaths when compared to standard of care in patients with severe COVID-19.

Who can participate?
Adult patients with severe COVID-19 (as per the WHO definition of severity) hospitalized at Sultan Qaboos University Hospital, Oman during the study recruitment period.

What does the study involve?
Eligible patients who provide written informed consent will be given the study drug anakinra in addition to standard treatment as defined by the hospital. Anakinra will be given as follows: 100 mg twice a day for 3 days, then 100 mg once daily for 7 days, all given via an injection into the fat layer between the skin and muscle.

What are the possible benefits and risks of participating?
Possible benefits include a decreased need for invasive mechanical ventilation and admission to the intensive care unit. Additionally, there may be decreased mortality from severe COVID-19 associated pneumonia.

Possible risks include injection site reactions, a rise in liver enzymes, and a decrease in neutrophil and or platelet count.

Where is the study run from?
The study takes place at Sultan Qaboos University Hospital (Oman)

When is the study starting and how long it is expected to run for?
From May 2020 to August 2020

Who is funding the study?
The study is funded by the Medical Research Center (Oman) with support from OQ (Oman).

Who is the main contact?
Dr Abdullah Balkhair
email: balkhair@squ.edu.om

Contact information

Dr Abdullah Balkhair
Scientific

Department of Medicine
Infectious Diseases Unit
Sultan Qaboos University Hospital
PO Box. 35
Alkoudh
Muscat
123
Oman

ORCiD logoORCID ID 0000-0001-6911-5568
Phone +968 24144935
Email balkhair@squ.edu.om
Dr Abdullah Balkhair
Public

Department of Medicine
Infectious Diseases Unit
Sultan Qaboos University Hospital
PO Box. 35
Alkoudh
Muscat
123
Oman

ORCiD logoORCID ID 0000-0001-6911-5568
Phone +968 24144935
Email balkhair@squ.edu.om

Study information

Study designSingle-center interventional study with a retrospectively derived historical control cohort as the comparator group.
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use contact details to request a participant information sheet
Scientific titleAnti-interleukin IL-1 receptor antagonist (anakinra) for the treatment of severe COVID-19 pneumonia and hyperinflammatory syndrome in patients admitted at Sultan Qaboos University Hospital
Study acronymOMA-COVID-19
Study objectivesAnakinra reduces need for invasive mechanical ventilation and deaths more than the standard of care in patients with severe COVID-19.
Ethics approval(s)Approved 15/06/2020, Medical Research Ethics Committee (College of Medicine and Health Sciences, Sultan Qaboos University, Oman. P.O Box 35. Al Khodh 123; + 968-24141103; mrec@squ.edu.om), ref: SQU-EC/169/2020 MREC #2136
Health condition(s) or problem(s) studiedSevere COVID-19 (SARS-CoV-2 infection)
InterventionEligible patients providing written informed consent will be administered anakinra (in addition to standard treatment as defined by the hospital protocols) via a subcutaneous route over 10 days as follows: 100 mg twice a day for 3 days, followed by 100 mg once daily for 7 days.

In patients on hemodialysis or with a glomerular filtration rate of less than 30 ml/min, the anakinra dosing schedule will be as follows: 100 mg once daily for 3 days, followed by 100 mg once every other day for 7 days via a subcutaneous route

A historical cohort retrospectively identified (fulfilling the same inclusion and exclusion criteria as the interventional arm and received the same standard of care) will be used as a comparator group.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Anakinra (brand name Kineret). Swedish Orphan Biovitrum, Stockholm, Sweden.
Primary outcome measure1. Need for invasive mechanical ventilation (IMV) or admission to the intensive care unit (ICU) is assessed from patient notes/records between baseline and 14 days
2. In-hospital mortality is assessed from patient notes/records between baseline and death or discharge
Secondary outcome measures1. Difference in the mean oxygen therapy requirements at baseline, 4 and 14 days
2. Change in the inflammatory biomarkers of disease severity (D-dimer, absolute lymphocyte count, serum ferritin, lactate dehydrogenase, c-reactive protein, and interleukin [IL-6] levels) measured using blood serum samples at baseline, 4 and 14 days
Overall study start date25/05/2020
Completion date15/08/2020

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants45 in the intervention arm AND 30 in the comparative historical control group
Total final enrolment75
Key inclusion criteria1. Aged >18 years
2. Admitted to the participating hospital with COVID-19 and any of the following:
2.1. Severe pneumonia defined as pneumonia and respiratory rate >30 breaths/min; or SpO2 <90% in room air or 93% or less under oxygen 6 l/min or more in addition to signs indicative of worsening respiratory function
2.2. Acute respiratory distress syndrome (ARDS) defined as pneumonia and bilateral opacities (on chest x-ray) and respiratory failure with PaO2/FiO2 ≤300 mmHg
Key exclusion criteria1. Known allergy to anakinra
2. Pregnant or breast-feeding women
3. Active or untreated TB
4. Apparent risk for gastrointestinal perforation (defined as recent [within 3 months] abdominal surgery, active inflammatory bowel disease, or active endoscopy-proven peptic ulcer disease)
5. Active cancer
6. Active bacterial or fungal infection
7. Chronic active liver disease
8. Absolute neutrophil count (ANC <1,500) or platelet count <50,000 /μl
Date of first enrolment15/06/2020
Date of final enrolment25/07/2020

Locations

Countries of recruitment

  • Oman

Study participating centre

Sultan Qaboos University Hospital
P.O Box 38
Al Khoudh
Muscat
123
Oman

Sponsor information

Sultan Qaboos University
University/education

Medical Research Center
Sultan Qaboos University
P.O. Box 83
Al-Khod
Muscat
123
Oman

Phone +968 24145923
Email khalid77@squ.edu.om
Website http://www.squ.edu.om/
ROR logo "ROR" https://ror.org/04wq8zb47

Funders

Funder type

Industry

OQ

No information available

Results and Publications

Intention to publish date31/10/2020
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planPlanned publication of the study results in a peer-reviewed journal.
IPD sharing planThe data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol file 04/08/2020 05/09/2020 No No
Results article results 01/02/2021 15/01/2021 Yes No

Additional files

ISRCTN74727214_PROTOCOL_04Aug20.pdf
Uploaded 05/09/2020

Editorial Notes

15/01/2021: Publication reference added.
05/09/2020: Uploaded protocol, 04 August 2020 (not peer reviewed).
08/08/2020: Trial’s existence confirmed by the Medical Research Ethics Committee, Sultan Qaboos University.