Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)

NCT ID: NCT05041907

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

3800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-30

Study Completion Date

2027-01-31

Brief Summary

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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.

Detailed Description

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The platform trial will assess drugs with potential SARS-CoV-2 antiviral activity of three general types:

A. Small molecule drugs: currently nitazoxanide, nirmatrelvir/ritonavir, hydroxychloroquine, atilotrelvir/ritonavir and metformin.

B. Monoclonal antibodies: Sotrovimab and any other monoclonal antibodies that become available. Monoclonal antibodies are vulnerable to viral escape mutations. Tracking their performance over time is important to characterise the impact and inform the therapeutics of mutant SARS-CoV-2 strains. This will also be important for other antivirals. Monoclonal antibodies are expensive and cannot be produced at large scale currently, but this may change in the near future. These drugs will be included if there is local availability and regulatory approval.

C. : Dose finding for the constituent parts of nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir has shown clinical efficacy in phase III studies, however, there are disadvantages to using it (drug-drug interactions, side effects, cost). In the urgent context of the pandemic, a higher dose of ritonavir was chosen to guarantee maximum boosting effect. We do not know if the maximal boosting effect could have been achieved with less, or even without ritonavir. It will be investigated whether reducing the doses of the constituent parts can still retain the effectiveness.

Randomization to the no antiviral treatment control arm (no intervention) will be fixed at a minimum of 20% throughout the study. The randomization ratios will be uniform for all available interventions.

Recruitment into the ivermectin arm was stopped on April 18th 2022 due to meeting the pre- defined stopping criteria.

Recruitment into the remdesivir arm was stopped on June 10th 2022 due to meeting the pre- defined stopping criteria.

Recruitment into the REGN-COV2 arm was stopped on October 20th 2022 due to meeting the pre-defined stopping criteria.

Recruitment into the favipiravir arm was stopped on October 31st 2022 due to meeting the pre-defined stopping criteria.

Recruitment into the molnupiravir arm was stopped on February 22nd 2023 due to meeting the pre-defined stopping criteria.

Recruitment into the fluoxetine arm was stopped on May 8th 2023 due to meeting the pre-defined stopping criteria.

Recruitment into the evusheld arm was stopped on July 4th 2023 due to meeting the pre-defined stopping criteria.

Recruitment into the ensitrelvir arm was stopped on April 21st 2024 due to meeting the pre-defined stopping criteria.

Recruitment into the combination molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™) arm was stopped on May 31st 2024 due to meeting the pre-defined stopping criteria.

Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Positive control: Nirmatrelvir/ritonavir (e.g. PAXLOVID™)

Group Type ACTIVE_COMPARATOR

Nirmatrelvir/ritonavir (e.g. PAXLOVID™)

Intervention Type DRUG

Nirmatrelvir 300mg BD for 5/7 Ritonavir 100mg BD for 5/7

Nitazoxanide

Group Type EXPERIMENTAL

Nitazoxanide

Intervention Type DRUG

Nitazoxanide 1.5g BD 7/7

Molnupiravir and Nirmatrelvir/ritonavir (e.g. PAXLOVID™) [This arm is now closed to recruitment]

Group Type EXPERIMENTAL

Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™)

Intervention Type DRUG

Molnupiravir 800mg BD for 5/7, Nirmatrelvir 300mg BD for 5/7, Ritonavir 100mg BD for 5/7

Hydroxychloroquine

Group Type EXPERIMENTAL

Hydroxychloroquine

Intervention Type DRUG

Hydroxychloroquine 400mg D0 BD and 400MG OD for a further 6/7

Negative control group

Group Type OTHER

No treatment

Intervention Type OTHER

No treatment (except antipyretics- paracetamol)

AZD7442 (EVUSHELD™) [This arm is now closed to recruitment]

Group Type EXPERIMENTAL

Monoclonal antibodies

Intervention Type DRUG

Monoclonal antibodies: 300mg tixagevimab/ 300 mg cilgavimab given once on D0

Fluoxetine [This arm is now closed to recruitment]

Group Type EXPERIMENTAL

Fluoxetine

Intervention Type DRUG

Fluoxetine 40mg OD for 7/7

Molnupiravir [This arm is now closed to recruitment]

Group Type EXPERIMENTAL

Molnupiravir

Intervention Type DRUG

Molnupiravir 800mg BD for 5/7

Sotrovimab [Pending addition]

Group Type EXPERIMENTAL

Sotrovimab

Intervention Type DRUG

Sotrovimab 500mg given once on D0

Ensitrelvir [This arm is now closed to recruitment]

Group Type EXPERIMENTAL

Ensitrelvir

Intervention Type DRUG

Ensitrelvir 375mg OD D0 and 125mg OD for a further 4/7

Positive control (REGN-COV2) [This arm is now closed to recruitment]

Group Type ACTIVE_COMPARATOR

Monoclonal antibodies

Intervention Type DRUG

Monoclonal antibodies: 600mg casirivimab/ 600mg imdevimab given once on D0

Favipiravir [This arm is now closed to recruitment]

Group Type EXPERIMENTAL

Favipiravir

Intervention Type DRUG

Favipiravir 1800mg BD D0 and 800mg BD for a further 6/7

Ivermectin [This arm is now closed to recruitment]

Group Type EXPERIMENTAL

Ivermectin

Intervention Type DRUG

Ivermectin 600micrograms/kg/day for 7/7.

Remdesivir [This arm is now closed to recruitment]

Group Type EXPERIMENTAL

Remdesivir

Intervention Type DRUG

Remdesivir 200mg D0 and 100mg for a further 4/7.

Atilotrelvir/ritonavir [Pending addition]

Group Type EXPERIMENTAL

Atilotrelvir/ritonavir

Intervention Type DRUG

Atilotrelvir 150mg BD for 5/7 Ritonavir 100mg BD for 5/7

Metformin (modified release) [Pending addition]

Group Type EXPERIMENTAL

Metformin

Intervention Type DRUG

Metformin 500mg TDS 5/7

Nirmatrelvir/ritonavir - 300/50 - dose finding [Pending addition]

Group Type EXPERIMENTAL

Nirmatrelvir/ritonavir

Intervention Type DRUG

Nirmatrelvir 300mg BD for 5/7 Ritonavir 50mg BD for 5/7

Nirmatrelvir/ritonavir - 150/50 - dose finding [Pending addition]

Group Type EXPERIMENTAL

Nirmatrelvir/ritonavir

Intervention Type DRUG

Nirmatrelvir 150mg BD for 5/7 Ritonavir 50mg BD for 5/7

Nirmatrelvir - dose finding [Pending addition]

Group Type EXPERIMENTAL

Nirmatrelvir

Intervention Type DRUG

Nirmatrelvir 300mg BD for 5/7

Interventions

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Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™)

Molnupiravir 800mg BD for 5/7, Nirmatrelvir 300mg BD for 5/7, Ritonavir 100mg BD for 5/7

Intervention Type DRUG

Hydroxychloroquine

Hydroxychloroquine 400mg D0 BD and 400MG OD for a further 6/7

Intervention Type DRUG

No treatment

No treatment (except antipyretics- paracetamol)

Intervention Type OTHER

Monoclonal antibodies

Monoclonal antibodies: 300mg tixagevimab/ 300 mg cilgavimab given once on D0

Intervention Type DRUG

Fluoxetine

Fluoxetine 40mg OD for 7/7

Intervention Type DRUG

Molnupiravir

Molnupiravir 800mg BD for 5/7

Intervention Type DRUG

Sotrovimab

Sotrovimab 500mg given once on D0

Intervention Type DRUG

Ensitrelvir

Ensitrelvir 375mg OD D0 and 125mg OD for a further 4/7

Intervention Type DRUG

Monoclonal antibodies

Monoclonal antibodies: 600mg casirivimab/ 600mg imdevimab given once on D0

Intervention Type DRUG

Favipiravir

Favipiravir 1800mg BD D0 and 800mg BD for a further 6/7

Intervention Type DRUG

Ivermectin

Ivermectin 600micrograms/kg/day for 7/7.

Intervention Type DRUG

Remdesivir

Remdesivir 200mg D0 and 100mg for a further 4/7.

Intervention Type DRUG

Atilotrelvir/ritonavir

Atilotrelvir 150mg BD for 5/7 Ritonavir 100mg BD for 5/7

Intervention Type DRUG

Metformin

Metformin 500mg TDS 5/7

Intervention Type DRUG

Nirmatrelvir/ritonavir

Nirmatrelvir 300mg BD for 5/7 Ritonavir 50mg BD for 5/7

Intervention Type DRUG

Nirmatrelvir/ritonavir

Nirmatrelvir 150mg BD for 5/7 Ritonavir 50mg BD for 5/7

Intervention Type DRUG

Nirmatrelvir

Nirmatrelvir 300mg BD for 5/7

Intervention Type DRUG

Nirmatrelvir/ritonavir (e.g. PAXLOVID™)

Nirmatrelvir 300mg BD for 5/7 Ritonavir 100mg BD for 5/7

Intervention Type DRUG

Nitazoxanide

Nitazoxanide 1.5g BD 7/7

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Universidade Federal de Minas Gerais

Minas Gerais, , Brazil

Site Status RECRUITING

Laos-Oxford-Mahosot Wellcome Trust Research Unit

Vientiane, , Laos

Site Status RECRUITING

Sukraraj Tropical & Infectious Disease Hospital

Kathmandu, , Nepal

Site Status RECRUITING

The Aga Khan University Hospital

Karachi, , Pakistan

Site Status TERMINATED

Vajira hospital

Bangkok, , Thailand

Site Status TERMINATED

Faculty of Tropical Medicine, Mahidol University

Bangkok, , Thailand

Site Status RECRUITING

Bangplee Hospital

Mueang Samut Prakan, , Thailand

Site Status TERMINATED

Countries

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Brazil Laos Nepal Pakistan Thailand

Central Contacts

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William Schilling, MD

Role: CONTACT

+662 203 6333

Nicholas J White, Prof.

Role: CONTACT

+662 203 6333

Facility Contacts

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Mauro Martins Teixeira

Role: primary

Koukeo Phommasone, PhD

Role: primary

+(85) 620 558 42842

Elizabeth Ashley, Professor

Role: backup

(+85)621 250 752

Abhilasha Karkey, Dr

Role: primary

Weerapong Phumratanaprapin, MD

Role: primary

References

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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.

Reference Type DERIVED
PMID: 41321979 (View on PubMed)

Schilling 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. 2025 Oct 10:S1473-3099(25)00482-7. doi: 10.1016/S1473-3099(25)00482-7. Online ahead of print.

Reference Type DERIVED
PMID: 41082886 (View on PubMed)

Jittamala 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.

Reference Type DERIVED
PMID: 39896880 (View on PubMed)

Wongnak 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.

Reference Type DERIVED
PMID: 38677300 (View on PubMed)

Luvira 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.

Reference Type DERIVED
PMID: 38225598 (View on PubMed)

Schilling 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. Erratum In: Lancet Infect Dis. 2023 Dec;23(12):e511. doi: 10.1016/S1473-3099(23)00649-7.

Reference Type DERIVED
PMID: 37778363 (View on PubMed)

Jittamala 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.

Reference Type DERIVED
PMID: 37470445 (View on PubMed)

Schilling 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.

Reference Type DERIVED
PMID: 36803992 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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VIR21001

Identifier Type: -

Identifier Source: org_study_id

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