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Trial record 1 of 1 for:    ivermectin | COVID-19 | Oxford
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Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV) (PLATCOV)

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ClinicalTrials.gov Identifier: NCT05041907
Recruitment Status : Recruiting
First Posted : September 13, 2021
Last Update Posted : September 8, 2022
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE September 7, 2021
First Posted Date  ICMJE September 13, 2021
Last Update Posted Date September 8, 2022
Actual Study Start Date  ICMJE September 30, 2021
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 2, 2022)
  • Rate of viral clearance for newly available and repurposed drugs [ Time Frame: Days 0-7 ]
    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 7 for each newly available and repurposed drug compared with the no antiviral treatment control i.e. those not receiving study drug
  • Rate of viral clearance for positive controls (e.g. monoclonal antibodies) [ Time Frame: Days 0-7 ]
    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 7 for positive controls (e.g. monoclonal antibodies) compared with the no antiviral treatment control i.e. those not receiving study drug
  • Rate of viral clearance for small novel molecule drugs [ Time Frame: Days 0-7 ]
    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 7 for small novel molecule drugs compared with the no antiviral treatment control i.e. those not receiving study drug
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2021)
  • Rate of viral clearance for repurposed drugs [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control
  • Rate of viral clearance of positive control (monoclonal antibodies) over time relative to the negative control [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control
  • Rate of viral clearance for small novel molecule drugs [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 2, 2022)
  • Viral kinetic levels in early COVID-19 disease [ Time Frame: Days 0-7 ]
    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 7 for each therapeutic arm compared with the no antiviral treatment control i.e. those not receiving study drug
  • Number of antiviral treatment arms that are shown to be effective i.e. a positive signal (>90% probability of >12.5% acceleration in viral clearance) [ Time Frame: Days 0-7 ]
    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 7 for each therapeutic arm compared with the no antiviral treatment control i.e. those not receiving study drug
  • Rates of viral clearance by treatment arm, as compared against REGN-COV2 (monoclonal antibody cocktail) monoclonal antibody cocktail) or other licensed and available therapeutics with evidence of accelerated viral clearance(monoclonal antibody cocktail) [ Time Frame: Days 0-7 ]
    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 7 for each therapeutic arm compared with positive control (e.g. REGN-COV-2 a monoclonal antibody cocktail) or other licensed and available therapeutics with evidence of accelerated viral clearance.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2021)
  • Viral kinetic levels in early COVID-19 disease [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control
  • Number of antiviral treatment arms that show a positive signal (>90% probability of >5% acceleration in viral clearance) [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control
  • Rates of viral clearance by treatment arm, as compared against REGN-COV2 (monoclonal antibody cocktail) [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control
Current Other Pre-specified Outcome Measures
 (submitted: September 2, 2022)
Rates of hospitalisation by treatment arm (hospitalisation for clinical reasons) [ Time Frame: Days 0-28 ]
Number of hospitalisations up to Day 28 in a treatment arm with an increased rate of viral clearance compared with the negative control i.e. patients not receiving study drug
Original Other Pre-specified Outcome Measures
 (submitted: September 10, 2021)
Rates of hospitalisation by treatment arm [ Time Frame: Days 0-28 ]
Number of hospitalisations up to Day 28 in a treatment arm with an increased rate of viral clearance compared with the negative control i.e. patients not receiving study drug
 
Descriptive Information
Brief Title  ICMJE Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
Official Title  ICMJE Finding Treatments for COVID-19: A Phase 2 Multi-centre Adaptive Platform Trial to Assess Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
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: Newly available and repurposed potential antiviral drugs; B: Positive control: monoclonal antibodies initially but subsequently any therapeutic that is shown to accelerate the rate of viral clearance C: Novel small molecule drugs that have gone through phase 1 testing

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:

A. Newly available and repurposed potential antiviral drugs. (initially from: hydroxychloroquine, ivermectin, lopinavir-ritonavir, miglustat, remdesivir, nitazoxanide, nebulized unfractionated heparin (UFH), favipiravir, Molnupiravir, Nirmatrelvir/ritonavir (e.g. PAXLOVID™), Fluoxetine, Fluvoxamine, AZD7442 (Evusheld),ensitrelvir, and a combination of Molnupiravir and Nirmatrelvir/ritonavir (e.g. PAXLOVID™)

Newly available and repurposed drugs are already used and recommended in some countries. Showing that they do not have significant antiviral activity is as important as showing that they do. For the newly approved antivirals, comparing antiviral activities in- vivo will inform health authorities' recommendations.

B. Positive control: monoclonal antibodies initially (e.g. casirivimab/imdevimab) but subsequently any therapeutic that is shown to accelerate the rate of viral clearance

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 may not be available early in the study, and will be included if there is local availability and regulatory approval.

C. Novel small molecule drugs that have gone through phase 1 testing Each site will include a negative control arm consisting of patients not receiving any study drug except for antipyretics- paracetamol. At any given time in the study, it is possible that not all intervention arms are available.

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

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: Favipiravir
    Favipiravir 1800mg BD D0 and 800mg BD for a further 6/7.
  • Drug: Monoclonal antibodies
    Monoclonal antibodies: 600mg casirivimab/ 600mg imdevimab given once on D0
  • Drug: Ivermectin
    Ivermectin 600micrograms/kg/day for 7/7.
  • Other: No treatment
    No treatment (except antipyretics- paracetamol)
  • Drug: Remdesivir
    Remdesivir 200mg D0 and 100mg for a further 4/7.
  • Drug: Fluoxetine
    Fluoxetine 40mg OD for 7/7
  • Drug: Molnupiravir
    Molnupiravir 800mg BD for 5/7
  • Drug: Nirmatrelvir/ritonavir (e.g. PAXLOVID™)
    Nirmatrelvir 300mg BD for 5/7 Ritonavir 100mg BD for 5/7
  • Drug: Nitazoxanide
    Nitazoxanide 1.5g BD 7/7
Study Arms  ICMJE
  • Active Comparator: Positive control (monoclonals)
    Intervention: Drug: Monoclonal antibodies
  • Experimental: Favipiravir
    Intervention: Drug: Favipiravir
  • Experimental: Ivermectin
    [This arm is now closed to recruitment]
    Intervention: Drug: Ivermectin
  • Experimental: Remdesivir
    [This arm is now closed to recruitment]
    Intervention: Drug: Remdesivir
  • Negative control group
    Intervention: Other: No treatment
  • Experimental: Fluoxetine
    Intervention: Drug: Fluoxetine
  • Experimental: Molnupiravir
    Intervention: Drug: Molnupiravir
  • Experimental: Nirmatrelvir/ritonavir (e.g. PAXLOVID™)
    Intervention: Drug: Nirmatrelvir/ritonavir (e.g. PAXLOVID™)
  • Experimental: Nitazoxanide
    Intervention: Drug: Nitazoxanide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 2, 2022)
1500
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2021)
750
Estimated Study Completion Date  ICMJE August 2024
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 50 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: William Schilling, MD +662 203 6333 william@tropmedres.ac
Contact: Nicholas J White, Prof. +662 203 6333 nickw@tropmedres.ac
Listed Location Countries  ICMJE Brazil,   Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05041907
Other Study ID Numbers  ICMJE VIR21001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

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).

Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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).

URL: http://wellcome.ac.uk/press-release/statement-data-sharing-public-health-emergencies
Current Responsible Party University of Oxford
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Oxford
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Oxford
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP