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

Phase 4

Completed

• Conditions: Treatment Efficacy
• Interventions: Combination Product: Niclosamide, Bromhexine; Combination Product: Fluvoxamine, Bromhexine; Combination Product: Fluvoxamine, Cyproheptadine; Drug: FluvoxaMINE Maleate 50 MG; Drug: Niclosamide Pill

• Registration Number: NCT05087381
• Lead Sponsor: Chulalongkorn University

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.

Study Timeline

• Study Start: 2021-10-01
• Study First Submitted: 2021-10-19
• Study First Submitted QC: 2021-10-19
• Study First Posted: 2021-10-21
• Primary Completion: 2022-06-21
• Study Completion: 2022-06-21
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-01
• Last Update Posted: 2022-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Niclosamide in Combination with Bromhexine Arm	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.
Fluvoxamine in Combination with Bromhexine Arm	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.
Fluvoxamine in Combination with Cyproheptadine Arm	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.
Fluvoxamine Arm	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.
Niclosamide Arm	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (3)

Chiangmai Neurological Hospital; 🇹🇭 Chiangmai, Thailand

Rajvithi Hospital; 🇹🇭 Ratchathewi, Bangkok, Thailand

Vibhavadi Hospital; 🇹🇭 Bangkok, Thailand