Back to resultsRandomized-controlled Trial of the Effectiveness of COVID-19 Early Treatment in Community
Primary Purpose
Treatment Efficacy
Status
Completed
Phase
Phase 4
Locations
Thailand
Study Type
Interventional
Intervention
FluvoxaMINE Maleate 50 MG
Fluvoxamine, Bromhexine
Fluvoxamine, Cyproheptadine
Niclosamide Pill
Niclosamide, Bromhexine
Sponsored by
About this trial
This is an interventional treatment trial for Treatment Efficacy focused on measuring COVID-19, Coronavirus, Treatment, Viral shedding, Coronavirus Infections, Respiratory Tract Infections, Anti-Infective Agents, Fluvoxamine, Bromhexine, Cyproheptadine, Niclosamide, Pneumonia, Viral, Early treatment
Eligibility Criteria
Inclusion Criteria:
- COVID-1 9 patients with mild symptoms and the results were confirmed by Antigen Test Kit or PCR for SARS-CoV-2.
- People who have symptoms consistent with COVID-19 and test positive for SARS-CoV-2 infection within 48 hours of being known.
- Participants are 18 years of age or older.
Exclusion Criteria:
- Almost recovered (generally much improved and symptoms now mild or almost absent)
- Judgement of the recruiting clinician deems ineligible.
- Previous randomisation to an arm of the trial
- Pregnancy
- Breastfeeding
- Known severe hepatic impairment.
- Known severe renal impairment.
- Currently taking Fluvoxamine, Bromhexine, Cyproheptadine, or Niclosamide
Sites / Locations
- Rajvithi Hospital
- Vibhavadi Hospital
- Chiangmai Neurological Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
No Intervention
Arm Label
Fluvoxamine Arm
Fluvoxamine in Combination with Bromhexine Arm
Fluvoxamine in Combination with Cyproheptadine Arm
Niclosamide Arm
Niclosamide in Combination with Bromhexine Arm
Usual Care Arm
Arm Description
The subjects received fluvoxamine (immediate release) 50 mg, 1 tablet in the morning and 50 mg 2 tablets before bedtime, orally after meals. For a total of 14 days, the first two days and the last two days, 50 mg 1 tablet in the morning and 50 mg 1 tablet at bedtime.
The subjects received fluvoxamine (immediate release) 50 mg, 1 tablet in the morning and 50 mg 2 tablets before bedtime, orally after meals. For a total of 14 days, the first two days and the last two days, 50 mg 1 tablet in the morning and 50 mg 1 tablet at bedtime. Co- administration with bromhexine 8 mg, 1 tablet twice taken after meals and taken at least 8 hours apart, for 10 days.
The subjects received fluvoxamine (immediate release) 50 mg, 1 tablet in the morning and 50 mg 2 tablets before bedtime, orally after meals. For a total of 14 days, the first two days and the last two days, 50 mg 1 tablet in the morning and 50 mg 1 tablet at bedtime. Co- administration with cyproheptadine 4 mg, 1 tablet, three times, orally after meals and should be taken every 8 hours apart, for 14 days.
The subjects received 1 tablet of niclosamide 1000 mg orally in divided doses twice a day. After meals in the morning and evening for a total of 14 days.
The subjects received 1 tablet of niclosamide 1000 mg orally in divided doses twice a day. After meals in the morning and evening for a total of 14 days. Co-administration with bromhexine 8 mg, 1 tablet twice taken after meals and taken at least 8 hours apart, for 10 days.
The control group received treatment according to the latest usual care medical guidelines provide by ministry of Thailand at that time.
Outcomes
Primary Outcome Measures
Hospital admission or mortality related to COVID-19
Contacts with health services reported by patients and/or captured by reports of patients' medical records
Time taken to self- report recovery
Patient reports the day they feel recovered
Progression to severe COVID-19 Disease
O2 saturation <92% on room air (in two consecutive measurements at least 2 hours apart) OR 2) requirement of hospitalization OR 3) need for artificial ventilation OR 4) death.
Secondary Outcome Measures
Reduction (change) in GI viral shedding (by PCR)
Fecal swabs
Change in respiratory viral clearance (by PCR)
Oropharyngeal swabs
Time to resolution of a fever
Online diary
Negative effects on well being
WHO 5 Well Being Index via online diary or telephone
Full Information
NCT ID
NCT05087381
First Posted
October 19, 2021
Last Updated
November 1, 2022
Sponsor
Chulalongkorn University
Collaborators
Rajavithi Hospital, Ministry of Health, Thailand, Mahidol University, Ramathibodi Hospital, QIMR Berghofer Medical Research Institute, Yamagata Prefectural Central Hospital, The University of Western Australia, Mae Fah Luang University, King Chulalongkorn Memorial Hospital, Washington University School of Medicine, Vibhavadi Hospital, Thanyarak Pattani Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05087381
Brief Title
Randomized-controlled Trial of the Effectiveness of COVID-19 Early Treatment in Community
Official Title
Randomized-controlled Trial of the Effectiveness of COVID-19 Early Treatment in Community With Fluvoxamine, Bromhexine, Cyproheptadine, and Niclosamide in Decreasing Recovery Time
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
June 21, 2022 (Actual)
Study Completion Date
June 21, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chulalongkorn University
Collaborators
Rajavithi Hospital, Ministry of Health, Thailand, Mahidol University, Ramathibodi Hospital, QIMR Berghofer Medical Research Institute, Yamagata Prefectural Central Hospital, The University of Western Australia, Mae Fah Luang University, King Chulalongkorn Memorial Hospital, Washington University School of Medicine, Vibhavadi Hospital, Thanyarak Pattani Hospital
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
There is an urgent need to identify effective treatments for SARS-CoV-2 infection that helps people recover quicker and reduces the need for hospital admission. The investigators develop an open, adaptive, platform trial to evaluate treatments, Fluvoxamine, Bromhexine, Cyproheptadine, and Niclosamide suitable for use in the community for treating COVID-like-illness that might help people recover sooner and prevent hospitalisation.
Detailed Description
There is an urgent need to identify interventions against COVID-19 suitable for wide use in the community that have been proven to be effective in reducing symptom duration or hospitalisation. There is urgent need to know whether potential COVID-19 treatments such as Fluvoxamine, Bromhexine, Cyproheptadine, and Niclosamide that are available for rapid pragmatic evaluation might modify the course of COVID-19 infections, particularly among those who are at higher risk of complications, such as those aged 50 years and over with comorbidity and those aged 65 years and over.
Most reported trials have been conducted in hospital settings, and there is little evidence from community settings, where most people with COVID-19 receive care and where deployment of effective early treatment could speed time to recovery and reduce complications. The investigators established a multi-arm, adaptive platform, randomised controlled trial for community treatment of COVID-19 syndromic illness in people at higher risk of an adverse illness course.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Efficacy
Keywords
COVID-19, Coronavirus, Treatment, Viral shedding, Coronavirus Infections, Respiratory Tract Infections, Anti-Infective Agents, Fluvoxamine, Bromhexine, Cyproheptadine, Niclosamide, Pneumonia, Viral, Early treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Open label, multiarm, prospective, randomised controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1200 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fluvoxamine Arm
Arm Type
Experimental
Arm Description
The subjects received fluvoxamine (immediate release) 50 mg, 1 tablet in the morning and 50 mg 2 tablets before bedtime, orally after meals. For a total of 14 days, the first two days and the last two days, 50 mg 1 tablet in the morning and 50 mg 1 tablet at bedtime.
Arm Title
Fluvoxamine in Combination with Bromhexine Arm
Arm Type
Experimental
Arm Description
The subjects received fluvoxamine (immediate release) 50 mg, 1 tablet in the morning and 50 mg 2 tablets before bedtime, orally after meals. For a total of 14 days, the first two days and the last two days, 50 mg 1 tablet in the morning and 50 mg 1 tablet at bedtime. Co- administration with bromhexine 8 mg, 1 tablet twice taken after meals and taken at least 8 hours apart, for 10 days.
Arm Title
Fluvoxamine in Combination with Cyproheptadine Arm
Arm Type
Experimental
Arm Description
The subjects received fluvoxamine (immediate release) 50 mg, 1 tablet in the morning and 50 mg 2 tablets before bedtime, orally after meals. For a total of 14 days, the first two days and the last two days, 50 mg 1 tablet in the morning and 50 mg 1 tablet at bedtime. Co- administration with cyproheptadine 4 mg, 1 tablet, three times, orally after meals and should be taken every 8 hours apart, for 14 days.
Arm Title
Niclosamide Arm
Arm Type
Experimental
Arm Description
The subjects received 1 tablet of niclosamide 1000 mg orally in divided doses twice a day. After meals in the morning and evening for a total of 14 days.
Arm Title
Niclosamide in Combination with Bromhexine Arm
Arm Type
Experimental
Arm Description
The subjects received 1 tablet of niclosamide 1000 mg orally in divided doses twice a day. After meals in the morning and evening for a total of 14 days. Co-administration with bromhexine 8 mg, 1 tablet twice taken after meals and taken at least 8 hours apart, for 10 days.
Arm Title
Usual Care Arm
Arm Type
No Intervention
Arm Description
The control group received treatment according to the latest usual care medical guidelines provide by ministry of Thailand at that time.
Intervention Type
Drug
Intervention Name(s)
FluvoxaMINE Maleate 50 MG
Other Intervention Name(s)
Telehealth monitoring
Intervention Description
The subjects received fluvoxamine (immediate release) 50 mg, 1 tablet in the morning and 50 mg 2 tablets before bedtime, orally after meals. For a total of 14 days, the first two days and the last two days, 50 mg 1 tablet in the morning and 50 mg 1 tablet at bedtime.
All enrolled patients will be provided a thermometer as well as a fingertip probe pulse oximeter, with the specific instructions to monitor both temperature at oxygen saturation at the time of daily oral administration of drug. In addition, Oropharyngeal swab samples will be collected for viral shedding as measured by PCR on days 0, 7 and 14. Fecal and blood samples will be collected for viral shedding as measured by PCR on days 0,7 and 14. A baseline fecal and oropharyngeal sample will be obtained on Day 0 prior to starting dosing of drugs.
Intervention Type
Combination Product
Intervention Name(s)
Fluvoxamine, Bromhexine
Other Intervention Name(s)
Telehealth monitoring
Intervention Description
The subjects received fluvoxamine (immediate release) 50 mg, 1 tablet in the morning and 50 mg 2 tablets before bedtime, orally after meals. For a total of 14 days, the first two days and the last two days, 50 mg 1 tablet in the morning and 50 mg 1 tablet at bedtime. Co- administration with bromhexine 8 mg, 1 tablet twice taken after meals and taken at least 8 hours apart, for 10 days.
All enrolled patients will be provided a thermometer as well as a fingertip probe pulse oximeter, with the specific instructions to monitor both temperature at oxygen saturation at the time of daily oral administration of drug. In addition, Oropharyngeal swab samples will be collected for viral shedding as measured by PCR on days 0, 7 and 14. Fecal and blood samples will be collected for viral shedding as measured by PCR on days 0,7 and 14. A baseline fecal and oropharyngeal sample will be obtained on Day 0 prior to starting dosing of drugs.
Intervention Type
Combination Product
Intervention Name(s)
Fluvoxamine, Cyproheptadine
Other Intervention Name(s)
Telehealth monitoring
Intervention Description
The subjects received fluvoxamine (immediate release) 50 mg, 1 tablet in the morning and 50 mg 2 tablets before bedtime, orally after meals. For a total of 14 days, the first two days and the last two days, 50 mg 1 tablet in the morning and 50 mg 1 tablet at bedtime. Co- administration with cyproheptadine 4 mg, 1 tablet, three times, orally after meals and should be taken every 8 hours apart, for 14 days.
All enrolled patients will be provided a thermometer as well as a fingertip probe pulse oximeter, with the specific instructions to monitor both temperature at oxygen saturation at the time of daily oral administration of drug. In addition, Oropharyngeal swab samples will be collected for viral shedding as measured by PCR on days 0, 7 and 14. Fecal and blood samples will be collected for viral shedding as measured by PCR on days 0,7 and 14. A baseline fecal and oropharyngeal sample will be obtained on Day 0 prior to starting dosing of drugs.
Intervention Type
Drug
Intervention Name(s)
Niclosamide Pill
Other Intervention Name(s)
Telehealth monitoring
Intervention Description
The subjects received 1 tablet of niclosamide 1000 mg orally in divided doses twice a day. After meals in the morning and evening for a total of 14 days.
All enrolled patients will be provided a thermometer as well as a fingertip probe pulse oximeter, with the specific instructions to monitor both temperature at oxygen saturation at the time of daily oral administration of drug. In addition, Oropharyngeal swab samples will be collected for viral shedding as measured by PCR on days 0, 7 and 14. Fecal and blood samples will be collected for viral shedding as measured by PCR on days 0,7 and 14. A baseline fecal and oropharyngeal sample will be obtained on Day 0 prior to starting dosing of drugs.
Intervention Type
Combination Product
Intervention Name(s)
Niclosamide, Bromhexine
Other Intervention Name(s)
Telehealth monitoring
Intervention Description
The subjects received 1 tablet of niclosamide 1000 mg orally in divided doses twice a day. After meals in the morning and evening for a total of 14 days. Co-administration with bromhexine 8 mg, 1 tablet twice taken after meals and taken at least 8 hours apart, for 10 days.
All enrolled patients will be provided a thermometer as well as a fingertip probe pulse oximeter, with the specific instructions to monitor both temperature at oxygen saturation at the time of daily oral administration of drug. In addition, Oropharyngeal swab samples will be collected for viral shedding as measured by PCR on days 0, 7 and 14. Fecal and blood samples will be collected for viral shedding as measured by PCR on days 0,7 and 14. A baseline fecal and oropharyngeal sample will be obtained on Day 0 prior to starting dosing of drugs.
Primary Outcome Measure Information:
Title
Hospital admission or mortality related to COVID-19
Description
Contacts with health services reported by patients and/or captured by reports of patients' medical records
Time Frame
Within 28 days
Title
Time taken to self- report recovery
Description
Patient reports the day they feel recovered
Time Frame
Enrolment through final day of participation
Title
Progression to severe COVID-19 Disease
Description
O2 saturation <92% on room air (in two consecutive measurements at least 2 hours apart) OR 2) requirement of hospitalization OR 3) need for artificial ventilation OR 4) death.
Time Frame
Enrolment through final day of participation
Secondary Outcome Measure Information:
Title
Reduction (change) in GI viral shedding (by PCR)
Description
Fecal swabs
Time Frame
Days 0,7,14
Title
Change in respiratory viral clearance (by PCR)
Description
Oropharyngeal swabs
Time Frame
Days 0,7,14
Title
Time to resolution of a fever
Description
Online diary
Time Frame
Enrolment through final day of participation
Title
Negative effects on well being
Description
WHO 5 Well Being Index via online diary or telephone
Time Frame
Days 0,7,15,28,60
Other Pre-specified Outcome Measures:
Title
Incidence of Adverse Events (AEs)
Description
Composite counts by Adverse Events and Serious Adverse Events
Time Frame
Enrolment through 30 days after final day of participation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
COVID-1 9 patients with mild symptoms and the results were confirmed by Antigen Test Kit or PCR for SARS-CoV-2.
People who have symptoms consistent with COVID-19 and test positive for SARS-CoV-2 infection within 48 hours of being known.
Participants are 18 years of age or older.
Exclusion Criteria:
Almost recovered (generally much improved and symptoms now mild or almost absent)
Judgement of the recruiting clinician deems ineligible.
Previous randomisation to an arm of the trial
Pregnancy
Breastfeeding
Known severe hepatic impairment.
Known severe renal impairment.
Currently taking Fluvoxamine, Bromhexine, Cyproheptadine, or Niclosamide
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dhammika Leshan Wannigama, MD PhD
Organizational Affiliation
Chulalongkorn University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Cameron Hurst, PhD
Organizational Affiliation
QIMR Berghofer Medical Research Institute
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Kanokpoj Chanpiwat, MD
Organizational Affiliation
Rajvithi Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Shuichi Abe, MD
Organizational Affiliation
Yamagata Prefectural Central Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Katika Akksilp, MD
Organizational Affiliation
Ministry of Health, Thailand
Official's Role
Study Director
Facility Information:
Facility Name
Rajvithi Hospital
City
Ratchathewi
State/Province
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Vibhavadi Hospital
City
Bangkok
ZIP/Postal Code
10900
Country
Thailand
Facility Name
Chiangmai Neurological Hospital
City
Chiangmai
ZIP/Postal Code
50200
Country
Thailand
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Randomized-controlled Trial of the Effectiveness of COVID-19 Early Treatment in Community
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