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| Name | Class |
|---|---|
| Department of Medical Services Ministry of Public Health of Thailand | OTHER_GOV |
| Ministry of Health, Thailand | OTHER_GOV |
| Mahidol University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fluvoxamine Arm | Experimental | 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. |
|
| Fluvoxamine in Combination with Bromhexine Arm | Experimental | 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 | Experimental | 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. |
|
| Niclosamide Arm | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FluvoxaMINE Maleate 50 MG | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Time taken to self- report recovery | Patient reports the day they feel recovered | Enrolment through final day of participation |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction (change) in GI viral shedding (by PCR) | Fecal swabs | Days 0,7,14 |
| Change in respiratory viral clearance (by PCR) | Oropharyngeal swabs |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse Events (AEs) | Composite counts by Adverse Events and Serious Adverse Events | Enrolment through 30 days after final day of participation |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dhammika Leshan Wannigama, MD PhD | Chulalongkorn University | Principal Investigator |
| 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 Chair |
| Katika Akksilp, MD | Ministry of Health, Thailand | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rajvithi Hospital | Ratchathewi | Bangkok | 10400 | Thailand | ||
| Vibhavadi Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38516100 | Derived | Wannigama DL, Hurst C, Phattharapornjaroen P, Hongsing P, Sirichumroonwit N, Chanpiwat K, Rad S M AH, Storer RJ, Ounjai P, Kanthawee P, Ngamwongsatit N, Kupwiwat R, Kupwiwat C, Brimson JM, Devanga Ragupathi NK, Charuluxananan S, Leelahavanichkul A, Kanjanabuch T, Higgins PG, Badavath VN, Amarasiri M, Verhasselt V, Kicic A, Chatsuwan T, Pirzada K, Jalali F, Reiersen AM, Abe S, Ishikawa H; COVID-EarlyMed Trial Team. Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial. EClinicalMedicine. 2024 Mar 14;70:102517. doi: 10.1016/j.eclinm.2024.102517. eCollection 2024 Apr. |
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| Ramathibodi Hospital |
| OTHER |
| QIMR Berghofer Medical Research Institute | OTHER |
| Yamagata Prefectural Central Hospital | UNKNOWN |
| The University of Western Australia | OTHER |
| Mae Fah Luang University | OTHER |
| King Chulalongkorn Memorial Hospital | OTHER |
| Washington University School of Medicine | OTHER |
| Vibhavadi Hospital | UNKNOWN |
| Thanyarak Pattani Hospital | UNKNOWN |
Open label, multiarm, prospective, randomised controlled trial
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| Niclosamide in Combination with Bromhexine Arm | Experimental | 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. |
|
| Usual Care Arm | No Intervention | The control group received treatment according to the latest usual care medical guidelines provide by ministry of Thailand at that time. |
|
|
| Fluvoxamine, Bromhexine | Combination Product | 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 | Combination Product | 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. |
|
|
| Niclosamide Pill | Drug | 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. |
|
|
| Niclosamide, Bromhexine | Combination Product | 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. |
|
|
| Days 0,7,14 |
| Time to resolution of a fever | Online diary | Enrolment through final day of participation |
| Negative effects on well being | WHO 5 Well Being Index via online diary or telephone | Days 0,7,15,28,60 |
| Bangkok |
| 10900 |
| Thailand |
| Chiangmai Neurological Hospital | Chiang Mai | 50200 | Thailand |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D018352 | Coronavirus Infections |
| D012141 | Respiratory Tract Infections |
| D011024 | Pneumonia, Viral |
| ID | Term |
|---|---|
| D011014 | Pneumonia |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D016666 | Fluvoxamine |
| D001964 | Bromhexine |
| D003533 | Cyproheptadine |
| D009534 | Niclosamide |
| ID | Term |
|---|---|
| D010091 | Oximes |
| D006898 | Hydroxylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D003514 | Cyclohexylamines |
| D003986 | Dibenzocycloheptenes |
| D001567 | Benzocycloheptenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D012458 | Salicylanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D012457 | Salicylamides |
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