COVID-19Phase 2PLATCOVNCT05041907
Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
A Phase 2 study testing Nirmatrelvir/ritonavir (e.g. PAXLOVID™), Nitazoxanide and Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™) in people with COVID-19, run by University of Oxford at 7 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Nirmatrelvir/ritonavir (e.g. PAXLOVID™), Nitazoxanide and Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,800 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 30 Sep 2021to Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
7 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
7 sites in 5 countries
Thailand3 sites, 1 recruiting
- Terminated
Vajira hospital
Bangkok, 10300
- Recruiting
Faculty of Tropical Medicine, Mahidol University
Bangkok, 10400
Weerapong Phumratanaprapin, MD, weerapong.phu@mahidol.ac.th
- Terminated
Bangplee Hospital
Mueang Samut Prakan, 10540
Brazil1 site, 1 recruiting
- Recruiting
Universidade Federal de Minas Gerais
Minas Gerais
Mauro Martins Teixeira, mmtex.ufmg@gmail.com
Laos1 site, 1 recruiting
- Recruiting
Laos-Oxford-Mahosot Wellcome Trust Research Unit
Vientiane, 01000
Koukeo Phommasone, PhD, +(85) 620 558 42842, Koukeo@tropmedres.ac
Elizabeth Ashley, Professor, (+85)621 250 752, liz@tropmedres.ac
Nepal1 site, 1 recruiting
- Recruiting
Sukraraj Tropical & Infectious Disease Hospital
Kathmandu
Abhilasha Karkey, Dr, akarkey@oucru.org
About this study
Official title: Finding Treatments for COVID-19: A Phase 2 Multi-centre Adaptive Platform Trial to Assess Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
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.
Read the detailed description
The platform trial will assess drugs with potential SARS-CoV-2 antiviral activity of three general types:
- Small molecule drugs: currently nitazoxanide, nirmatrelvir/ritonavir, hydroxychloroquine, atilotrelvir/ritonavir and metformin.
- 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.
- : 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
- COVID-19
- Being tested
- Nirmatrelvir/ritonavir (e.g. PAXLOVID™), Nitazoxanide, Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™), Hydroxychloroquine, No treatment
- Keywords
- COVID-19, Phase 2, Antiviral Pharmacodynamics
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nirmatrelvir/ritonavir (e.g. PAXLOVID™)Drug
Nirmatrelvir 300mg BD for 5/7 Ritonavir 100mg BD for 5/7
NitazoxanideDrug
Nitazoxanide 1.5g BD 7/7
Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™)Drug
Molnupiravir 800mg BD for 5/7, Nirmatrelvir 300mg BD for 5/7, Ritonavir 100mg BD for 5/7
Hydroxychloroquine 400mg D0 BD and 400MG OD for a further 6/7
No treatmentOther
No treatment (except antipyretics- paracetamol)
Monoclonal antibodiesDrug
Monoclonal antibodies: 300mg tixagevimab/ 300 mg cilgavimab given once on D0
FluoxetineDrug
Fluoxetine 40mg OD for 7/7
MolnupiravirDrug
Molnupiravir 800mg BD for 5/7
SotrovimabDrug
Sotrovimab 500mg given once on D0
EnsitrelvirDrug
Ensitrelvir 375mg OD D0 and 125mg OD for a further 4/7
Monoclonal antibodiesDrug
Monoclonal antibodies: 600mg casirivimab/ 600mg imdevimab given once on D0
FavipiravirDrug
Favipiravir 1800mg BD D0 and 800mg BD for a further 6/7
IvermectinDrug
Ivermectin 600micrograms/kg/day for 7/7.
RemdesivirDrug
Remdesivir 200mg D0 and 100mg for a further 4/7.
Atilotrelvir/ritonavirDrug
Atilotrelvir 150mg BD for 5/7 Ritonavir 100mg BD for 5/7
MetforminDrug
Metformin 500mg TDS 5/7
Nirmatrelvir/ritonavirDrug
Nirmatrelvir 300mg BD for 5/7 Ritonavir 50mg BD for 5/7
Nirmatrelvir/ritonavirDrug
Nirmatrelvir 150mg BD for 5/7 Ritonavir 50mg BD for 5/7
NirmatrelvirDrug
Nirmatrelvir 300mg BD for 5/7
| Study group | Role | What they receive |
|---|---|---|
| Positive control: Nirmatrelvir/ritonavir (e.g. PAXLOVID™) | Active comparator | Not described Receives: Drug: Nirmatrelvir/ritonavir (e.g. PAXLOVID™) |
| Nitazoxanide | Experimental | Not described Receives: Drug: Nitazoxanide |
| Molnupiravir and Nirmatrelvir/ritonavir (e.g. PAXLOVID™) [This arm is now closed to recruitment] | Experimental | Not described Receives: Drug: Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™) |
| Hydroxychloroquine | Experimental | Not described Receives: Drug: Hydroxychloroquine |
| Negative control group | Other | Not described Receives: Other: No treatment |
| AZD7442 (EVUSHELD™) [This arm is now closed to recruitment] | Experimental | Not described Receives: Drug: Monoclonal antibodies |
| Fluoxetine [This arm is now closed to recruitment] | Experimental | Not described Receives: Drug: Fluoxetine |
| Molnupiravir [This arm is now closed to recruitment] | Experimental | Not described Receives: Drug: Molnupiravir |
| Sotrovimab [Pending addition] | Experimental | Not described Receives: Drug: Sotrovimab |
| Ensitrelvir [This arm is now closed to recruitment] | Experimental | Not described Receives: Drug: Ensitrelvir |
| Positive control (REGN-COV2) [This arm is now closed to recruitment] | Active comparator | Not described Receives: Drug: Monoclonal antibodies |
| Favipiravir [This arm is now closed to recruitment] | Experimental | Not described Receives: Drug: Favipiravir |
| Ivermectin [This arm is now closed to recruitment] | Experimental | Not described Receives: Drug: Ivermectin |
| Remdesivir [This arm is now closed to recruitment] | Experimental | Not described Receives: Drug: Remdesivir |
| Atilotrelvir/ritonavir [Pending addition] | Experimental | Not described Receives: Drug: Atilotrelvir/ritonavir |
| Metformin (modified release) [Pending addition] | Experimental | Not described Receives: Drug: Metformin |
| Nirmatrelvir/ritonavir - 300/50 - dose finding [Pending addition] | Experimental | Not described Receives: Drug: Nirmatrelvir/ritonavir |
| Nirmatrelvir/ritonavir - 150/50 - dose finding [Pending addition] | Experimental | Not described Receives: Drug: Nirmatrelvir/ritonavir |
| Nirmatrelvir - dose finding [Pending addition] | Experimental | Not described Receives: Drug: Nirmatrelvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: Days 0-5
Secondary outcomes (4)
Viral kinetic levels in early COVID-19 disease
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 therapeutic arm compared with the no antiviral treatment control i.e., those not receiving study drug
Measured: 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).
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 therapeutic arm compared with the no antiviral treatment control i.e., those not receiving study drug
Measured: Days 0-5
Viral rebound of studied treatment arms in comparison to contemporaneous controls (e.g. no study drug arm, positive control)
After stopping treatment for at least 24 hours (or 5 days if no drug is given or a single dose monoclonal antibody is given), rebound is defined as an oropharyngeal eluate viral density estimate >1000 genomes per ml for at least 1 timepoint (average 2 swabs), after >2 consecutive days of average daily viral density estimate less than 100 genomes per ml
Measured: Days 6-14
Rates of fever clearance and symptom resolution with respect to no treatment
The following endpoints will be used:
- Time to resolution of fever
- Area Under the Curve of recorded temperature
- Time to resolution of symptoms
Measured: Days 0-14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2021
- Study start30 Sep 2021
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05041907
- Sponsor's protocol ID
- VIR21001
- Acronym
- PLATCOV
- Status last verified
- Jan 2026
- First submitted
- 7 Sep 2021
- Last updated
- 19 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Publications
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.
PubMed 41321979Schilling 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.
PubMed 41082886Jittamala 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.
PubMed 39896880Wongnak 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.
PubMed 38677300Luvira 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.
PubMed 38225598Schilling 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.
PubMed 37778363Jittamala 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.
PubMed 37470445Schilling 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.
PubMed 36803992
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Finding Treatments for COVID-19: A Phase 2 Multi-centre Adaptive Platform Trial to Assess Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
- ClinicalTrials.gov ID
- NCT05041907
- Acronym / sponsor ID
- PLATCOV / VIR21001
- Conditions
- COVID-19
- Keywords
- COVID-19, Phase 2, Antiviral Pharmacodynamics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 3,800 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 30 Sep 2021 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 13 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
The platform trial will assess drugs with potential SARS-CoV-2 antiviral activity of three general types:
- Small molecule drugs: currently nitazoxanide, nirmatrelvir/ritonavir, hydroxychloroquine, atilotrelvir/ritonavir and metformin.
- 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.
- : 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 19
| Arm | Type | Receives |
|---|---|---|
| Positive control: Nirmatrelvir/ritonavir (e.g. PAXLOVID™) | Active comparator | Drug: Nirmatrelvir/ritonavir (e.g. PAXLOVID™) |
| Nitazoxanide | Experimental | Drug: Nitazoxanide |
| Molnupiravir and Nirmatrelvir/ritonavir (e.g. PAXLOVID™) [This arm is now closed to recruitment] | Experimental | Drug: Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™) |
| Hydroxychloroquine | Experimental | Drug: Hydroxychloroquine |
| Negative control group | Other | Other: No treatment |
| AZD7442 (EVUSHELD™) [This arm is now closed to recruitment] | Experimental | Drug: Monoclonal antibodies |
| Fluoxetine [This arm is now closed to recruitment] | Experimental | Drug: Fluoxetine |
| Molnupiravir [This arm is now closed to recruitment] | Experimental | Drug: Molnupiravir |
| Sotrovimab [Pending addition] | Experimental | Drug: Sotrovimab |
| Ensitrelvir [This arm is now closed to recruitment] | Experimental | Drug: Ensitrelvir |
| Positive control (REGN-COV2) [This arm is now closed to recruitment] | Active comparator | Drug: Monoclonal antibodies |
| Favipiravir [This arm is now closed to recruitment] | Experimental | Drug: Favipiravir |
| Ivermectin [This arm is now closed to recruitment] | Experimental | Drug: Ivermectin |
| Remdesivir [This arm is now closed to recruitment] | Experimental | Drug: Remdesivir |
| Atilotrelvir/ritonavir [Pending addition] | Experimental | Drug: Atilotrelvir/ritonavir |
| Metformin (modified release) [Pending addition] | Experimental | Drug: Metformin |
| Nirmatrelvir/ritonavir - 300/50 - dose finding [Pending addition] | Experimental | Drug: Nirmatrelvir/ritonavir |
| Nirmatrelvir/ritonavir - 150/50 - dose finding [Pending addition] | Experimental | Drug: Nirmatrelvir/ritonavir |
| Nirmatrelvir - dose finding [Pending addition] | Experimental | Drug: Nirmatrelvir |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nirmatrelvir/ritonavir (e.g. PAXLOVID™)Nirmatrelvir 300mg BD for 5/7 Ritonavir 100mg BD for 5/7 | Drug | Positive control: Nirmatrelvir/ritonavir (e.g. PAXLOVID™) |
| NitazoxanideNitazoxanide 1.5g BD 7/7 | Drug | Nitazoxanide |
| 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 | Drug | Molnupiravir and Nirmatrelvir/ritonavir (e.g. PAXLOVID™) [This arm is now closed to recruitment] |
| HydroxychloroquineHydroxychloroquine 400mg D0 BD and 400MG OD for a further 6/7 | Drug | Hydroxychloroquine |
| No treatmentNo treatment (except antipyretics- paracetamol) | Other | Negative control group |
| Monoclonal antibodiesMonoclonal antibodies: 300mg tixagevimab/ 300 mg cilgavimab given once on D0 | Drug | AZD7442 (EVUSHELD™) [This arm is now closed to recruitment] |
| FluoxetineFluoxetine 40mg OD for 7/7 | Drug | Fluoxetine [This arm is now closed to recruitment] |
| MolnupiravirMolnupiravir 800mg BD for 5/7 | Drug | Molnupiravir [This arm is now closed to recruitment] |
| SotrovimabSotrovimab 500mg given once on D0 | Drug | Sotrovimab [Pending addition] |
| EnsitrelvirEnsitrelvir 375mg OD D0 and 125mg OD for a further 4/7 | Drug | Ensitrelvir [This arm is now closed to recruitment] |
| Monoclonal antibodiesMonoclonal antibodies: 600mg casirivimab/ 600mg imdevimab given once on D0 | Drug | Positive control (REGN-COV2) [This arm is now closed to recruitment] |
| FavipiravirFavipiravir 1800mg BD D0 and 800mg BD for a further 6/7 | Drug | Favipiravir [This arm is now closed to recruitment] |
| IvermectinIvermectin 600micrograms/kg/day for 7/7. | Drug | Ivermectin [This arm is now closed to recruitment] |
| RemdesivirRemdesivir 200mg D0 and 100mg for a further 4/7. | Drug | Remdesivir [This arm is now closed to recruitment] |
| Atilotrelvir/ritonavirAtilotrelvir 150mg BD for 5/7 Ritonavir 100mg BD for 5/7 | Drug | Atilotrelvir/ritonavir [Pending addition] |
| MetforminMetformin 500mg TDS 5/7 | Drug | Metformin (modified release) [Pending addition] |
| Nirmatrelvir/ritonavirNirmatrelvir 300mg BD for 5/7 Ritonavir 50mg BD for 5/7 | Drug | Nirmatrelvir/ritonavir - 300/50 - dose finding [Pending addition] |
| Nirmatrelvir/ritonavirNirmatrelvir 150mg BD for 5/7 Ritonavir 50mg BD for 5/7 | Drug | Nirmatrelvir/ritonavir - 150/50 - dose finding [Pending addition] |
| NirmatrelvirNirmatrelvir 300mg BD for 5/7 | Drug | Nirmatrelvir - dose finding [Pending addition] |
Primary outcome
Rate of viral clearance for interventions relative to the no study arm (This is a superiority comparison)
Time frame: Days 0-5
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
Rate of viral clearance for interventions relative to the positive control arm (This is a non-inferiority or superiority comparison).
Time frame: Days 0-5
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)
4 secondary outcomes
Viral kinetic levels in early COVID-19 disease
Time frame: 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).
Time frame: Days 0-5
Viral rebound of studied treatment arms in comparison to contemporaneous controls (e.g. no study drug arm, positive control)
Time frame: Days 6-14
Rates of fever clearance and symptom resolution with respect to no treatment
Time frame: Days 0-14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2026.
- Derived from this study: PubMed 41321979Kaewkhao 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.
- Derived from this study: PubMed 41082886Schilling 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.
- Derived from this study: PubMed 39896880Jittamala 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.
- Derived from this study: PubMed 38677300Wongnak 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.
- Derived from this study: PubMed 38225598Luvira 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.
- Derived from this study: PubMed 37778363Schilling 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.
- Derived from this study: PubMed 37470445Jittamala 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.
- Derived from this study: PubMed 36803992Schilling 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.
- Individual participant dataSharing planned: Yes. 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).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nirmatrelvir/ritonavir (e.g. PAXLOVID™), Nitazoxanide and Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™) in people with COVID-19, run by University of Oxford at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Thailand, Brazil, Laos, Nepal, Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact William Schilling, MD (+662 203 6333, william@tropmedres.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of viral clearance for interventions relative to the no study arm (This is a superiority comparison) (time frame: Days 0-5). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05041907, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.