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

Treatment Efficacy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05087381
• Other study ID #: 64197
• Status: Completed
• Phase: Phase 4
• Start date: October 1, 2021
• Est. completion date: June 21, 2022

Study information

• Verified date: November 2022
• Source: Chulalongkorn University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1200
• Est. completion date: June 21, 2022
• Est. primary completion date: June 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Treatment Efficacy

Intervention

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.

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.
• 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.

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.

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.

Locations

Country	Name	City	State
Thailand	Vibhavadi Hospital	Bangkok
Thailand	Chiangmai Neurological Hospital	Chiangmai
Thailand	Rajvithi Hospital	Ratchathewi	Bangkok

Sponsors (13)

Lead Sponsor	Collaborator
Chulalongkorn University	King Chulalongkorn Memorial Hospital, Mae Fah Luang University, Mahidol University, Ministry of Health, Thailand, QIMR Berghofer Medical Research Institute, Rajavithi Hospital, Ramathibodi Hospital, Thanyarak Pattani Hospital, The University of Western Australia, Vibhavadi Hospital, Washington University School of Medicine, Yamagata Prefectural Central Hospital

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of Adverse Events (AEs)	Composite counts by Adverse Events and Serious Adverse Events	Enrolment through 30 days after final day of participation
Primary	Hospital admission or mortality related to COVID-19	Contacts with health services reported by patients and/or captured by reports of patients' medical records	Within 28 days
Primary	Time taken to self- report recovery	Patient reports the day they feel recovered	Enrolment through final day of participation
Primary	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.	Enrolment through final day of participation
Secondary	Reduction (change) in GI viral shedding (by PCR)	Fecal swabs	Days 0,7,14
Secondary	Change in respiratory viral clearance (by PCR)	Oropharyngeal swabs	Days 0,7,14
Secondary	Time to resolution of a fever	Online diary	Enrolment through final day of participation
Secondary	Negative effects on well being	WHO 5 Well Being Index via online diary or telephone	Days 0,7,15,28,60