Randomized-controlled Trial of the Effectiveness of COVID-19 Early Treatment in Community

Sponsor

Chulalongkorn University (Other)

Overall Status

Completed

CT.gov ID

NCT05087381

Collaborator

Rajavithi Hospital (Other), Ministry of Health, Thailand (Other), Mahidol University (Other), Ramathibodi Hospital (Other), QIMR Berghofer Medical Research Institute (Other), Yamagata Prefectural Central Hospital (Other), The University of Western Australia (Other), Mae Fah Luang University (Other), King Chulalongkorn Memorial Hospital (Other), Washington University School of Medicine (Other), Vibhavadi Hospital (Other)

1,200

Enrollment

Locations

Arms

8.6

Actual Duration (Months)

400

Patients Per Site

46.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Treatment Efficacy	Drug: FluvoxaMINE Maleate 50 MG Combination Product: Fluvoxamine, Bromhexine Combination Product: Fluvoxamine, Cyproheptadine Drug: Niclosamide Pill Combination Product: Niclosamide, Bromhexine	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Open label, multiarm, prospective, adaptive platform, randomised controlled trialOpen label, multiarm, prospective, adaptive platform, randomised controlled trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 1, 2021

Actual Primary Completion Date :

Jun 21, 2022

Actual Study Completion Date :

Jun 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluvoxamine Arm 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.	Drug: FluvoxaMINE Maleate 50 MG 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. Other Names: Telehealth monitoring
Experimental: Fluvoxamine in Combination with Bromhexine Arm 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.	Combination Product: Fluvoxamine, Bromhexine 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. Other Names: Telehealth monitoring
Experimental: Fluvoxamine in Combination with Cyproheptadine Arm 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.	Combination Product: Fluvoxamine, Cyproheptadine 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. Other Names: Telehealth monitoring
Experimental: Niclosamide Arm 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.	Drug: Niclosamide Pill 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. Other Names: Telehealth monitoring
Experimental: Niclosamide in Combination with Bromhexine Arm 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.	Combination Product: Niclosamide, Bromhexine 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. Other Names: Telehealth monitoring
No Intervention: Usual Care Arm The control group received treatment according to the latest usual care medical guidelines provide by ministry of Thailand at that time.

Outcome Measures

Primary Outcome Measures

Hospital admission or mortality related to COVID-19 [Within 28 days]
Contacts with health services reported by patients and/or captured by reports of patients' medical records
Time taken to self- report recovery [Enrolment through final day of participation]
Patient reports the day they feel recovered
Progression to severe COVID-19 Disease [Enrolment through final day of participation]
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) [Days 0,7,14]
Fecal swabs
Change in respiratory viral clearance (by PCR) [Days 0,7,14]
Oropharyngeal swabs
Time to resolution of a fever [Enrolment through final day of participation]
Online diary
Negative effects on well being [Days 0,7,15,28,60]
WHO 5 Well Being Index via online diary or telephone

Other Outcome Measures

Incidence of Adverse Events (AEs) [Enrolment through 30 days after final day of participation]
Composite counts by Adverse Events and Serious Adverse Events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rajvithi Hospital	Ratchathewi	Bangkok	Thailand	10400
2	Vibhavadi Hospital	Bangkok		Thailand	10900
3	Chiangmai Neurological Hospital	Chiangmai		Thailand	50200

Investigators

Principal Investigator: Dhammika Leshan Wannigama, MD PhD, Chulalongkorn University
Study Chair: Cameron Hurst, PhD, QIMR Berghofer Medical Research Institute
Study Chair: Kanokpoj Chanpiwat, MD, Rajvithi Hospital
Study Chair: Shuichi Abe, MD, Yamagata Prefectural Central Hospital
Study Director: Katika Akksilp, MD, Ministry of Health, Thailand