Fight COVID-19 Trial (FIGHT-COVID-19)

• ClinicalTrials.gov Identifier: NCT04303299
• Recruitment Status: Completed
• First Posted: March 11, 2020
• Last Update Posted: September 2, 2021
• Sponsor: Rajavithi Hospital
• Information provided by (Responsible Party): Dr Subsai Kongsaengdao, Rajavithi Hospital

Study Description

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

Condition or disease	Intervention/treatment	Phase
SARS-COV-2 Infections; COVID-19	Drug: Oral	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 320 participants
• 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
• Official Title: 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
• Actual Study Start Date: August 19, 2020
• Actual Primary Completion Date: August 28, 2021
• Actual Study Completion Date: August 28, 2021

Arms and Interventions

Arm	Intervention/treatment
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	Drug: Oral; Anti virus treatment
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	Drug: Oral; Anti virus treatment
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	Drug: Oral; Anti virus treatment
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	Drug: Oral; Anti virus treatment
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	Drug: Oral; Anti virus treatment
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	Drug: Oral; Anti virus treatment
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	Drug: Oral; Anti virus treatment
No Intervention: Conventional Qurantine; Patient who unwilling to treatment and willing to quarantine in mild COVID19

Outcome Measures

Primary Outcome Measures :

1. SARS-CoV-2 eradication time [ Time Frame: Up to 24 weeks ]
   Eradication of nasopharyngeal SARS-CoV-2

Secondary Outcome Measures :

1. Number of patient with Death [ Time Frame: Up to 24 weeks ]
   Any death after treatment adjusted by initial severity in each arm
2. 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
3. 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
4. Number of patient developed Acute Respiratory Distress Syndrome After treatment [ Time Frame: Up to 24 weeks ]
   Number of patient developed new ARDS

Other Outcome Measures:

1. Number of patient with Acute Respiratory Distress Syndrome Recovery [ Time Frame: Up to 24 weeks ]
   Acute Respiratory Distress Syndrome Recovery rate
2. Time to recovery [ Time Frame: Up to 24 Weeks ]
   The time to recovery was defined as the time between the first day of antiviral treatment or hospitalization to the day when there was no further requirement for antiviral medication or on-going medical care or the day of discharge from the hospital.

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 100 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Thailand

Assistant Professor Subsai Kongsaengdao

Bangkok, Thailand, 10400

Sponsors and Collaborators

Rajavithi Hospital

More Information

Study Data/Documents: Data references 

Identifier: Thai government data

News 

Reference review data set of DMS database 

Preliminary Database result of prospective open study of 119 pneumonia ( another population)patient ( it is not data from this RCT)

Reference News 

• Responsible Party: Dr Subsai Kongsaengdao, Associate Professor, Rajavithi Hospital
• ClinicalTrials.gov Identifier: NCT04303299
• Other Study ID Numbers: TH-DMS-COVID19 study
• First Posted: March 11, 2020
• Last Update Posted: September 2, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases