Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
PLATCOV
1 other identifier
interventional
3,800
5 countries
7
Brief Summary
The trial will develop and validate a platform for quantitative assessment of antiviral effects in low-risk patients with high viral burdens and uncomplicated COVID-19 to determine in-vivo antiviral activity. In this randomized open label, controlled, group sequential adaptive platform trial, we will assess the performance of three distinct types of intervention relative to control (no treatment): A: Small molecule drugs; B: Monoclonal antibodies; C: Dose finding for the constituent parts of nirmatrelvir/ritonavir PLATCOV study is supported by the Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 covid19
Started Sep 2021
Longer than P75 for phase_2 covid19
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 7, 2021
CompletedFirst Posted
Study publicly available on registry
September 13, 2021
CompletedStudy Start
First participant enrolled
September 30, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2027
February 19, 2026
January 1, 2026
5.3 years
September 7, 2021
February 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Rate of viral clearance for interventions relative to the no study arm (This is a superiority comparison)
Rate of viral clearance- estimated from the log10 viral density derived from qPCR of standardised duplicate oropharyngeal swabs/ saliva taken daily from baseline (day 0) to day 5 for each intervention compared with the no antiviral treatment control i.e., those not receiving study drug
Days 0-5
Rate of viral clearance for interventions relative to the positive control arm (This is a non-inferiority or superiority comparison).
Rate of viral clearance- estimated from the log10 viral density derived from qPCR of standardised duplicate oropharyngeal swabs/ saliva taken daily from baseline (day 0) to day 5 for interventions compared with the current best antiviral treatment option (accelerated viral clearance relative to the positive control arm)
Days 0-5
Secondary Outcomes (4)
Viral kinetic levels in early COVID-19 disease
Days 0-5
Optimal dosing regimens through pharmacometric assessment for antiviral drugs with evidence of efficacy in the literature or from the trial data (e.g., Nirmatrelvir/ritonavir, Ensitrelvir etc).
Days 0-5
Viral rebound of studied treatment arms in comparison to contemporaneous controls (e.g. no study drug arm, positive control)
Days 6-14
Rates of fever clearance and symptom resolution with respect to no treatment
Days 0-14
Other Outcomes (2)
Rates of hospitalisation by treatment arm (hospitalisation for clinical reasons)
Days 0-28
Relationship between viral clearance, randomisation arm and other measures (covariates) and development of post- acute COVID-19 (i.e. long COVID)
Days 0-120
Study Arms (19)
Positive control: Nirmatrelvir/ritonavir (e.g. PAXLOVID™)
ACTIVE COMPARATORNitazoxanide
EXPERIMENTALMolnupiravir and Nirmatrelvir/ritonavir (e.g. PAXLOVID™) [This arm is now closed to recruitment]
EXPERIMENTALHydroxychloroquine
EXPERIMENTALNegative control group
OTHERAZD7442 (EVUSHELD™) [This arm is now closed to recruitment]
EXPERIMENTALFluoxetine [This arm is now closed to recruitment]
EXPERIMENTALMolnupiravir [This arm is now closed to recruitment]
EXPERIMENTALSotrovimab [Pending addition]
EXPERIMENTALEnsitrelvir [This arm is now closed to recruitment]
EXPERIMENTALPositive control (REGN-COV2) [This arm is now closed to recruitment]
ACTIVE COMPARATORFavipiravir [This arm is now closed to recruitment]
EXPERIMENTALIvermectin [This arm is now closed to recruitment]
EXPERIMENTALRemdesivir [This arm is now closed to recruitment]
EXPERIMENTALAtilotrelvir/ritonavir [Pending addition]
EXPERIMENTALMetformin (modified release) [Pending addition]
EXPERIMENTALNirmatrelvir/ritonavir - 300/50 - dose finding [Pending addition]
EXPERIMENTALNirmatrelvir/ritonavir - 150/50 - dose finding [Pending addition]
EXPERIMENTALNirmatrelvir - dose finding [Pending addition]
EXPERIMENTALInterventions
Nirmatrelvir 300mg BD for 5/7 Ritonavir 100mg BD for 5/7
Hydroxychloroquine 400mg D0 BD and 400MG OD for a further 6/7
Ensitrelvir 375mg OD D0 and 125mg OD for a further 4/7
Monoclonal antibodies: 300mg tixagevimab/ 300 mg cilgavimab given once on D0
Favipiravir 1800mg BD D0 and 800mg BD for a further 6/7
Ivermectin 600micrograms/kg/day for 7/7.
Remdesivir 200mg D0 and 100mg for a further 4/7.
Atilotrelvir 150mg BD for 5/7 Ritonavir 100mg BD for 5/7
Nirmatrelvir 300mg BD for 5/7 Ritonavir 50mg BD for 5/7
Molnupiravir 800mg BD for 5/7, Nirmatrelvir 300mg BD for 5/7, Ritonavir 100mg BD for 5/7
Eligibility Criteria
You may qualify if:
- Patient understands the procedures and requirements and is willing and able to give informed consent for full participation in the study.
- Previously healthy adults, male or female, aged 18 to 60 years at time of consent with early symptomatic COVID-19
- SARS-CoV-2 positive by lateral flow antigen test OR a positive PCR test for SARS-CoV-2 within the last 24hrs with a Ct value of less than 25 (all viral targets)
- Symptoms of COVID-19 (including fever, or history of fever) for less than 4 days (96 hours).
- Oxygen saturation ≥96% measured by pulse-oximetry at time of screening.
- Able to walk unaided and unimpeded in ADLs
- Agrees and is able to adhere to all study procedures, including availability and contact information for follow-up visits
You may not qualify if:
- The patient may not enter the study if ANY of the following apply:
- Taking any concomitant medications or drugs (see appendix 4)†
- Presence of any chronic illness/ condition requiring long term treatment, or other significant comorbidity (e.g. diabetes, obesity but see appendix 4 for the full list)
- Laboratory abnormalities discovered at screening (see appendix 4)
- For females: pregnancy, actively trying to become pregnant, or lactation
- Contraindication to taking, or known hypersensitivity reaction to any of the proposed therapeutics (see appendix 4)
- Currently participating in another COVID-19 therapeutic or vaccine trial
- Evidence of pneumonia (although imaging is NOT required)
- healthy women on the oral contraceptive pill are eligible to join the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Universidade Federal de Minas Gerais
Minas Gerais, Brazil
Laos-Oxford-Mahosot Wellcome Trust Research Unit
Vientiane, 01000, Laos
Sukraraj Tropical & Infectious Disease Hospital
Kathmandu, Nepal
The Aga Khan University Hospital
Karachi, Pakistan
Vajira hospital
Bangkok, 10300, Thailand
Faculty of Tropical Medicine, Mahidol University
Bangkok, 10400, Thailand
Bangplee Hospital
Mueang Samut Prakan, 10540, Thailand
Related Publications (8)
Kaewkhao N, Tarning J, Blessborn D. LC-MS/MS Method Validation for Quantification of Nirmatrelvir in Human Plasma. Int J Anal Chem. 2025 Nov 17;2025:6625833. doi: 10.1155/ianc/6625833. eCollection 2025.
PMID: 41321979DERIVEDSchilling WHK, Jittamala P, Wongnak P, Watson JA, Boyd S, Luvira V, Siripoon T, Ngamprasertchai T, Batty EM, Beer E, Singh S, Asawasriworanan T, Seers T, Phommasone K, Evans TJ, Kruabkontho V, Ngernseng T, Tubprasert J, Abdad MY, Madmanee W, Kouhathong J, Suwannasin K, Pagornrat W, Piteekan T, Hanboonkunupakarn B, Poovorawan K, Potaporn M, Srisubat A, Loharjun B, Chotivanich K, Imwong M, Pukrittayakamee S, Dondorp AM, Day NPJ, Piyaphanee W, Phumratanaprapin W, White NJ; PLATCOV Collaborative Group. Antiviral efficacy of oral ensitrelvir versus oral ritonavir-boosted nirmatrelvir in COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial. Lancet Infect Dis. 2026 Feb;26(2):139-147. doi: 10.1016/S1473-3099(25)00482-7. Epub 2025 Oct 11.
PMID: 41082886DERIVEDJittamala P, Boyd S, Schilling WHK, Watson JA, Ngamprasertchai T, Siripoon T, Luvira V, Batty EM, Wongnak P, Esper LM, Almeida PJ, Cruz C, Ascencao FR, Aguiar RS, Ghanchi NK, Callery JJ, Singh S, Kruabkontho V, Ngernseng T, Tubprasert J, Madmanee W, Suwannasin K, Promsongsil A, Hanboonkunupakarn B, Poovorawan K, Potaporn M, Srisubat A, Loharjun B, Taylor WRJ, Qamar F, Kazi AM, Beg MA, Chommanam D, Vidhamaly S, Chotivanich K, Imwong M, Pukrittayakamee S, Dondorp AM, Day NPJ, Teixeira MM, Piyaphanee W, Phumratanaprapin W, White NJ; PLATCOV Collaborative Group. Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV). EClinicalMedicine. 2025 Jan 18;80:103036. doi: 10.1016/j.eclinm.2024.103036. eCollection 2025 Feb.
PMID: 39896880DERIVEDWongnak P, Schilling WHK, Jittamala P, Boyd S, Luvira V, Siripoon T, Ngamprasertchai T, Batty EM, Singh S, Kouhathong J, Pagornrat W, Khanthagan P, Hanboonkunupakarn B, Poovorawan K, Mayxay M, Chotivanich K, Imwong M, Pukrittayakamee S, Ashley EA, Dondorp AM, Day NPJ, Teixeira MM, Piyaphanee W, Phumratanaprapin W, White NJ, Watson JA; PLATCOV Collaborative Group. Temporal changes in SARS-CoV-2 clearance kinetics and the optimal design of antiviral pharmacodynamic studies: an individual patient data meta-analysis of a randomised, controlled, adaptive platform study (PLATCOV). Lancet Infect Dis. 2024 Sep;24(9):953-963. doi: 10.1016/S1473-3099(24)00183-X. Epub 2024 Apr 24.
PMID: 38677300DERIVEDLuvira V, Schilling WHK, Jittamala P, Watson JA, Boyd S, Siripoon T, Ngamprasertchai T, Almeida PJ, Ekkapongpisit M, Cruz C, Callery JJ, Singh S, Tuntipaiboontana R, Kruabkontho V, Ngernseng T, Tubprasert J, Abdad MY, Keayarsa S, Madmanee W, Aguiar RS, Santos FM, Hanboonkunupakarn P, Hanboonkunupakarn B, Poovorawan K, Imwong M, Taylor WRJ, Chotivanich V, Chotivanich K, Pukrittayakamee S, Dondorp AM, Day NPJ, Teixeira MM, Piyaphanee W, Phumratanaprapin W, White NJ; PLATCOV Collaborative Group. Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial. BMC Infect Dis. 2024 Jan 15;24(1):89. doi: 10.1186/s12879-023-08835-3.
PMID: 38225598DERIVEDSchilling WHK, Jittamala P, Watson JA, Boyd S, Luvira V, Siripoon T, Ngamprasertchai T, Batty EM, Cruz C, Callery JJ, Singh S, Saroj M, Kruabkontho V, Ngernseng T, Tanglakmankhong N, Tubprasert J, Abdad MY, Madmanee W, Kouhathong J, Suwannasin K, Pagornrat W, Piaraksa N, Hanboonkunupakarn P, Hanboonkunupakarn B, Poovorawan K, Potaporn M, Srisubat A, Loharjun B, Taylor WRJ, Chotivanich V, Chotivanich K, Imwong M, Pukrittayakamee S, Dondorp AM, Day NPJ, Teixeira MM, Piyaphanee W, Phumratanaprapin W, White NJ; PLATCOV Collaborative Group. Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial. Lancet Infect Dis. 2024 Jan;24(1):36-45. doi: 10.1016/S1473-3099(23)00493-0. Epub 2023 Sep 28.
PMID: 37778363DERIVEDJittamala P, Schilling WHK, Watson JA, Luvira V, Siripoon T, Ngamprasertchai T, Almeida PJ, Ekkapongpisit M, Cruz C, Callery JJ, Boyd S, Anunsittichai O, Hongsuwan M, Singhaboot Y, Pagornrat W, Tuntipaiboontana R, Kruabkontho V, Ngernseng T, Tubprasert J, Abdad MY, Keayarsa S, Madmanee W, Aguiar RS, Santos FM, Batty EM, Hanboonkunupakarn P, Hanboonkunupakarn B, Sookprome S, Poovorawan K, Imwong M, Taylor WRJ, Chotivanich V, Sangketchon C, Ruksakul W, Chotivanich K, Pukrittayakamee S, Dondorp AM, Day NPJ, Teixeira MM, Piyaphanee W, Phumratanaprapin W, White NJ; PLATCOV Collaborative Group. Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV). J Infect Dis. 2023 Nov 11;228(10):1318-1325. doi: 10.1093/infdis/jiad275.
PMID: 37470445DERIVEDSchilling WHK, Jittamala P, Watson JA, Ekkapongpisit M, Siripoon T, Ngamprasertchai T, Luvira V, Pongwilai S, Cruz C, Callery JJ, Boyd S, Kruabkontho V, Ngernseng T, Tubprasert J, Abdad MY, Piaraksa N, Suwannasin K, Hanboonkunupakarn P, Hanboonkunupakarn B, Sookprome S, Poovorawan K, Thaipadungpanit J, Blacksell S, Imwong M, Tarning J, Taylor WRJ, Chotivanich V, Sangketchon C, Ruksakul W, Chotivanich K, Teixeira MM, Pukrittayakamee S, Dondorp AM, Day NPJ, Piyaphanee W, Phumratanaprapin W, White NJ; PLATCOV Collaborative Group. Pharmacometrics of high-dose ivermectin in early COVID-19 from an open label, randomized, controlled adaptive platform trial (PLATCOV). Elife. 2023 Feb 21;12:e83201. doi: 10.7554/eLife.83201.
PMID: 36803992DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 7, 2021
First Posted
September 13, 2021
Study Start
September 30, 2021
Primary Completion (Estimated)
January 1, 2027
Study Completion (Estimated)
January 1, 2027
Last Updated
February 19, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- CSR, ANALYTIC CODE
- Time Frame
- after the main paper has been published
- Access Criteria
- MORU Data Sharing Policy https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing. The criteria for authorship will be consistent with the international guidelines (http://www.icmje.org/#author).
With patient's consent, clinical data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with other researchers to use in the future. Data generated from this study will adhere to the 2016 "Statement on data sharing in public health emergencies"(https://wellcome.ac.uk/press-release/statement-data-sharing-public-health-emergencies).