Treatment Efficacy
Conditions
Keywords
COVID-19, Coronavirus, Treatment, Viral shedding, Coronavirus Infections, Respiratory Tract Infections, Anti-Infective Agents, Fluvoxamine, Bromhexine, Cyproheptadine, Niclosamide, Pneumonia, Viral, Early treatment
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.
Interventions
DRUGFluvoxaMINE 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_PRODUCTFluvoxamine, 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.
COMBINATION_PRODUCTFluvoxamine, 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.
DRUGNiclosamide 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_PRODUCTNiclosamide, 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.
Sponsors
Department of Medical Services Ministry of Public Health of Thailand
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
Chulalongkorn University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label, multiarm, prospective, randomised controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) | Enrolment through 30 days after final day of participation | Composite counts by Adverse Events and Serious Adverse Events |
Countries
Thailand
Outcome results
None listed