Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Various Combination of Protease Inhibitors, Oseltamivir, Favipiravir, and Hydroxychloroquine for Treatment of COVID-19 : A Randomized Control Trial (THDMS-COVID-19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04303299
Recruitment Status : Not yet recruiting
First Posted : March 11, 2020
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Dr Subsai Kongsaengdao, Rajavithi Hospital

Tracking Information
First Submitted Date  ICMJE February 24, 2020
First Posted Date  ICMJE March 11, 2020
Last Update Posted Date June 16, 2020
Estimated Study Start Date  ICMJE July 15, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2020)
SARS-CoV-2 eradication time [ Time Frame: Up to 24 weeks ]
Eradication of nasopharyngeal SARS-CoV-2
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Number of patient with Death [ Time Frame: Up to 24 weeks ]
    Any death after treatment adjusted by initial severity in each arm
  • Number of patient with Recovery adjusted by initial severity in each arm [ Time Frame: Up to 24 weeks ]
    Normal pulmonary function, normal O2 saturation after treatment Adjusted by initial severity in each arm
  • Number of day With ventilator dependent adjusted by initial severity in each arm [ Time Frame: Up to 24 weeks ]
    Number of day with ventilator assistant
  • Number of patient developed Acute Respiratory Distress Syndrome After treatment [ Time Frame: Up to 24 weeks ]
    Number of patient developed new ARDS
Original Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2020)
  • Death [ Time Frame: Up to 24 weeks ]
    Any death
  • Recovery rate [ Time Frame: Up to 24 weeks ]
    Normal pulmonary function
  • ventilator dependent [ Time Frame: Up to 24 weeks ]
    Number of day with ventilator assistant
  • Acute Respiratory Distress Syndrome Rate [ Time Frame: Up to 24 weeks ]
    Number of patient developed new ARDS
Current Other Pre-specified Outcome Measures
 (submitted: March 10, 2020)
Number of patient with Acute Respiratory Distress Syndrome Recovery [ Time Frame: Up to 24 weeks ]
Acute Respiratory Distress Syndrome Recovery rate
Original Other Pre-specified Outcome Measures
 (submitted: March 8, 2020)
Acute Respiratory Distress Syndrome Recovery rate [ Time Frame: Up to 24 weeks ]
Acute Respiratory Distress Syndrome Recovery rate
 
Descriptive Information
Brief Title  ICMJE Various Combination of Protease Inhibitors, Oseltamivir, Favipiravir, and Hydroxychloroquine for Treatment of COVID-19 : A Randomized Control Trial
Official Title  ICMJE A 6 Week Prospective, Open Label, Randomized, in Multicenter Study of, Oseltamivir Plus Hydroxychloroquine Versus Lopipinavir/ Ritonavir Plus Oseltamivir Versus Darunavir/ Ritonavir Plus Oseltamivir Plus Hydroxychloroquine in Mild COVID-19 AND Lopipinavir/ Ritonavir Plus Oseltamivir Versus Favipiravir Plus Lopipinavir / Ritonavir Versus Darunavir/ Ritonavir Plus Oseltamivir Plus Hydroxychloroquine Versus Favipiravir Plus Darunavir and Ritonavir Plus Hydroxychloroquine in Moderate to Critically Ill COVID-19
Brief Summary A 6-Week Prospective, Open label, Randomized, in Multicenter Study of, Oseltamivir 300mg per day plus Hydroxychloroquine 800 mg per day versus Combination of Lopipinavir 800mg (or 10 mg/kg ) per day and Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Oseltamivir 300 mg ( or 4-6 mg /kg ) per day versus Combination of Darunavir 400 mg every 8 hours plus ritonavir 200 mg (or 2.5 mg/kg ) per day plus Oseltamivir 300mg ( or 4-6 mg /kg ) per day plus Hydroxychloroquine 400 mg per day in mild COVID-19 and Combination of Lopipinavir 800 mg (or 10 mg/kg ) per day and Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Oseltamivir 300 mg ( or 4-6 mg /kg ) per day versus Favipiravir 2400 mg, 2400 mg, and 1200 mg every 8 h on day 1, and a maintenance dose of 1200 mg twice a day plus Lopipinavir 800 mg ( or 10 mg/kg ) per day and Ritonavir 200 mg ( or 2.5 mg/kg ) per day versus Combination of Darunavir 400 mg every 8 hours plus ritonavir 200 mg (or 2.5 mg/kg ) plus Oseltamivir 300 mg (or 4-6 mg /kg ) per day plus Hydroxychloroquine 400 mg per day versus Favipiravir 2400 mg, 2400 mg, and 1200 mg every 8 h on day 1, and a maintenance dose of 1200 mg twice a day plus Darunavir 400 mg every 8 hours Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Hydroxychloroquine 400 mg per day in moderate to critically illness in COVID-19
Detailed Description

Overall Study Design and Plan Various Combination of Protease inhibitors, Oseltamivir, Favipiravir, and Chloroquin for treatment of COVID-19. Non parametric and parametric statistical analysis will be analysed in the efficacy of treatment. For the pair-wise comparison, 2-sided p-value was used to ensure that the overall Type I error=0.05. Beta error 80%. Demographic and safety analyses were based on the summary of descriptive statistics.

Pre-randomization Phase The pre-randomization phase consisted of a screening period (0 to 1 day prior to randomization).

Screening Period (Day -1 to 0) At the screening visit and prior to performance of any study procedures, the investigators would explain the details of the study and the subject would have to sign on the written informed consent, exclusion criteria, and inclusion criteria Each subject who was willing to enrol into the study was asked about their medical history as well as their recent and current medications being taken. All enrolled subjects were asked to undertake an initial physical examination and had to satisfy the criteria for the inclusion /exclusion before being enrolled into the study.

All patients were asked to complete physical examination, CXR, CBC plt, proBNP, High sensitive C reactive protein and Laboratory blood (livers tests, haematology,) examinations, urine pregnancy test) were performed amount 5.5 mL for safety reasons. Nasopharyngeal swabs were collected to detect the ORF 1ab and E genes (sensitivity: 1000 copies per milliliter) by polymerase chain reactions. Will be performed The inclusion visit included the following examination and tests: - physical examination,- vital signs,- weight,- CBC laboratory test result,-Chest X ray or CT chest Blood for plasma cytokine assay -Pro BNP and High sensitive C reactive protein, D dimer Treatment period All patient will be treated with specific arm for 10-14 days or until negative for Nasopharyngeal swabs were collected to detect the ORF 1ab and E genes of SARS -CoV-2 for 3 consecutive tests every 24 -48 hours. ECG monitoring for prolonged QTcB in Hydroxychloroquine arm will be closed monitored The quarantine period will be performed for 7-14 days after swab negative All cases may be treated with Antibiotics as prophylaxis or specific treatment Other standard treatment will be allowed for investigator judgments. CXR nasoparyngeal swab will be performed every 1-2 days or up to investigator judgments Follow up Visits Patient will be check up CXR and CT scan, nasoparyngeal swab will be performed every 1-2 day until negative test and until 4-6 weeks or clinical complete recovery.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:

The study is described as 'open' unblinded, however all clinical, virological and laboratory data, as well as adverse events were reviewed by two independent physicians, and all radiological images were reviewed by two independent radiologists who were blinded to the treatment assignments.

The study outcomes assessed blinded to randomized group ( PROBE design - prospective randomised open blinded evaluation)

Primary Purpose: Treatment
Condition  ICMJE
  • SARS-COV-2 Infections
  • COVID-19
Intervention  ICMJE Drug: Oral
Anti virus treatment
Study Arms  ICMJE
  • Experimental: Oseltamivir plus Chloroquine in Mild COVID19
    Oseltamivir 300mg ( or 4-6 mg/kg) per day plus Hydroxychloroquine 800 mg per day In mild COVID19
    Intervention: Drug: Oral
  • Experimental: Darunavir and Ritonavir plus oseltamivir
    Darunavir 400 mg every 8 hours Ritonavir 200 mg (or 2.5 mg/kg ) per day plus plus Oseltamivir 300mg ( or 4-6 mg/kg) per day plus Hydroxychloroquine 400mg per day in Mild COVID19
    Intervention: Drug: Oral
  • Experimental: Lopinavir and Ritonavir plus Oseltamivir in mild COVID19
    Lopinavir 800 mg ( or 10 mg/kg ) per day and Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Oseltamivir 300 mg ( or 4-6 mg /kg ) per day In mild COVID19
    Intervention: Drug: Oral
  • Experimental: Lopinavir and Ritonavir Oseltamivir moderate to severe COVID19
    Lopinavir 800 mg ( or 10 mg/kg ) per day and Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Oseltamivir 300 mg ( or 4-6 mg /kg ) per day In moderate to critically ill COVID19
    Intervention: Drug: Oral
  • Experimental: Favipiravir lopinavir /Ritonavir for mod. To severe
    Lopinavir 800 mg (or 10 mg/kg ) per day and Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Favipiravir 2400 mg, 2400 mg, and 1200 mg every 8 h on day 1, and a maintenance dose of 1200 mg twice a day in Mild COVID19 In moderate to critically ill COVID19
    Intervention: Drug: Oral
  • Experimental: Darunavir /ritonavir oseltamivir chloroquine mod-severe
    Darunavir 400 mg every 8 hours Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Oseltamivir 300 mg (or 4-6 mg /kg ) per day plus Hydroxychloroquine 400 mg per day In moderate to critically ill COVID19
    Intervention: Drug: Oral
  • Experimental: Darunavir /ritonavir favipiravir chloroquine mod-severe
    Darunavir 400 mg every 8 hours Ritonavir 200 mg ( or 2.5 mg/kg ) per day plus Favipiravir 2400 mg, 2400 mg, and 1200 mg every 8 h on day 1, and a maintenance dose of 1200 mg twice a day plus Hydroxychloroquine 400 mg per day In moderate to critically ill COVID19
    Intervention: Drug: Oral
  • No Intervention: Conventional Qurantine
    Patient who unwilling to treatment and willing to quarantine in mild COVID19
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 8, 2020)
320
Original Estimated Enrollment  ICMJE
 (submitted: March 8, 2020)
80
Estimated Study Completion Date  ICMJE March 30, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • The subject has to grant permission to enter into the study by signing and dating the informed consent form before completing any study-related procedure such as any assessment or evaluation not related to the normal medical care of the subject.
  • Able to give written inform consent and retained one copy of the consent form
  • Male or female subject, aged between 16 - 100 years old.
  • Subject diagnosed to be COVID19
  • Female subject in good health and sexually active was instructed by the investigator to avoid pregnancy during the study and to use condom or other contraceptive measure if necessary. The subject was required to have a negative urine pregnancy test before being eligible for the study. (At each of the subsequent visit, a urine pregnancy test was performed).
  • Subject judged to be reliable for compliance for taking medication and capable of recording the effects of the medication and motivated in receiving benefits from the treatment.and compliance to quarantine procedure 7-14 days after treatment

Exclusion Criteria:

  • The subject was pregnant or lactating.
  • The subject was a female at risk of pregnancy during the study and not taking adequate precautions against pregnancy.
  • The subject had a known hypersensitivity to any of the test materials or related compounds.
  • The subject was unable or unwilling to comply fully with the protocol.
  • Treatment with investigational drug (s) within 6 months before the screening visit.
  • The subject had previously entered in this study.
  • Patient who planned to schedule elective surgery during the study
  • The used of other antiviral agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 100 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Subsai Kongsaengdao, M.D. 66818180890 skhongsa@gmail.com
Contact: Narumol Sawanpanyalert, M.D., M.P.H 66818424148 thailandemt2019@gmail.com
Listed Location Countries  ICMJE Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04303299
Other Study ID Numbers  ICMJE TH-DMS-COVID19 study
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
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Dr Subsai Kongsaengdao, Rajavithi Hospital
Study Sponsor  ICMJE Rajavithi Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Rajavithi Hospital
Verification Date June 2020

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