Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: A randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU)
Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: A randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU)
Background: after admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission.
Methods: in a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n = 192) or SoC only (n = 195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data.
Results: adherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P = 0.063); PP 40.7% RRR, 9.6% ARR (P = 0.017); AT 43.2% RRR, 10.8% ARR (P = 0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events.
Conclusions: in hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.
COVID-19, Doxycycline, Hospitalization, Humans, Intensive Care Units, SARS-CoV-2, Treatment Outcome
e0280745
Dhar, Raja
67e26853-5b52-46f6-8238-97e31eeed21f
Kirkpatrick, John
bd488b71-f361-4171-b7e5-01f0063bb09f
Gilbert, Laura
ceb76903-f42b-4c9f-a476-1b32e8646e01
Khanna, Arjun
0eda5b30-5e28-41da-b02e-4353cbebaf38
Modi, Mahavir Madhavdas
3745023f-aefa-4db3-85f8-aac3f3ec456c
Chawla, Rakesh K
cee8226e-9cbe-4965-a24d-9d40b0c828fb
Dalal, Sonia
40804504-c90f-4c53-8578-4d0dd13ceabe
Maturu, Venkata Nagarjuna
2553945d-31d9-452c-8d8d-391006356770
Stern, Marcel
395a2263-7185-42a1-80cc-4eb9565d9873
Keppler, Oliver T
d1470f24-dd1a-4246-afa7-d9d98d04ff23
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Gadola, Stephan D
ef2fa6cf-2ccc-4fea-a7a5-cc03a9d13ab1
23 January 2023
Dhar, Raja
67e26853-5b52-46f6-8238-97e31eeed21f
Kirkpatrick, John
bd488b71-f361-4171-b7e5-01f0063bb09f
Gilbert, Laura
ceb76903-f42b-4c9f-a476-1b32e8646e01
Khanna, Arjun
0eda5b30-5e28-41da-b02e-4353cbebaf38
Modi, Mahavir Madhavdas
3745023f-aefa-4db3-85f8-aac3f3ec456c
Chawla, Rakesh K
cee8226e-9cbe-4965-a24d-9d40b0c828fb
Dalal, Sonia
40804504-c90f-4c53-8578-4d0dd13ceabe
Maturu, Venkata Nagarjuna
2553945d-31d9-452c-8d8d-391006356770
Stern, Marcel
395a2263-7185-42a1-80cc-4eb9565d9873
Keppler, Oliver T
d1470f24-dd1a-4246-afa7-d9d98d04ff23
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Gadola, Stephan D
ef2fa6cf-2ccc-4fea-a7a5-cc03a9d13ab1
Dhar, Raja, Kirkpatrick, John, Gilbert, Laura, Khanna, Arjun, Modi, Mahavir Madhavdas, Chawla, Rakesh K, Dalal, Sonia, Maturu, Venkata Nagarjuna, Stern, Marcel, Keppler, Oliver T, Djukanovic, Ratko and Gadola, Stephan D
(2023)
Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: A randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU).
PLoS ONE, 18 (1), , [e0280745].
(doi:10.1371/journal.pone.0280745).
Abstract
Background: after admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission.
Methods: in a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n = 192) or SoC only (n = 195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data.
Results: adherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P = 0.063); PP 40.7% RRR, 9.6% ARR (P = 0.017); AT 43.2% RRR, 10.8% ARR (P = 0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events.
Conclusions: in hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.
Text
journal.pone.0280745
- Version of Record
More information
Accepted/In Press date: 19 December 2022
Published date: 23 January 2023
Additional Information:
Copyright: © 2023 Dhar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding Information:
RDh received an unrestricted grant (grant/study code: IIS/11/20) over Rs 500’000.00, corresponding to USD 6730.00) from Cipla (https://www.cipla.com) to finance a part-time study coordinator for this trial. Cipla had no role in the trial design, data collection, data analysis, data interpretation, or writing of the manuscript. We wish to acknowledge the following clinicians who, as members of the clinical teams attending to the patient participants on this trial, contributed to clinical management of the patients and data collection: Dr Dipabali Acharjee, Research Associate, CMRI hospital, Kolkata, India. Dr Virender Pratibh Prasad, Consultant Pulmonary Medicine, Yashoda Hospital, Somajiguda, India. Dr Aditya K. Chawla, Junior Consultant, Saroj Superspeciality Hospital and Jaipur Golden Hospital, Delhi and ii. Dr Gaurav Chaudhary, DNB Resident (Final yr), Jaipur Golden Hospital, Delhi, India. Dr Vishnu Gireesh, Resident, Department of Chest Medicine, Ruby Hall Clinic, Pune, India. Dr Avhinav Bhosle, Consultant Pulmonologist, Kalyan Hospital, Vadodara, India. Dr Viswesvaran Balasubramanian, Lead Consultant and Head, Department of Pulmonary and Sleep Medicine, Yashoda hospitals, Hyderabad
Publisher Copyright:
© 2023 Dhar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords:
COVID-19, Doxycycline, Hospitalization, Humans, Intensive Care Units, SARS-CoV-2, Treatment Outcome
Identifiers
Local EPrints ID: 475181
URI: http://eprints.soton.ac.uk/id/eprint/475181
ISSN: 1932-6203
PURE UUID: 5a489adc-a0a1-4763-bbb5-032e4c0b272d
Catalogue record
Date deposited: 13 Mar 2023 17:50
Last modified: 17 Mar 2024 02:34
Export record
Altmetrics
Contributors
Author:
Raja Dhar
Author:
John Kirkpatrick
Author:
Laura Gilbert
Author:
Arjun Khanna
Author:
Mahavir Madhavdas Modi
Author:
Rakesh K Chawla
Author:
Sonia Dalal
Author:
Venkata Nagarjuna Maturu
Author:
Marcel Stern
Author:
Oliver T Keppler
Author:
Stephan D Gadola
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
