NCT05087381

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,200

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Oct 2021

Shorter than P25 for phase_4

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2021

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

October 19, 2021

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 21, 2021

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 21, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 21, 2022

Completed
Last Updated

November 4, 2022

Status Verified

November 1, 2022

Enrollment Period

9 months

First QC Date

October 19, 2021

Last Update Submit

November 1, 2022

Conditions

Keywords

COVID-19CoronavirusTreatmentViral sheddingCoronavirus InfectionsRespiratory Tract InfectionsAnti-Infective AgentsFluvoxamineBromhexineCyproheptadineNiclosamidePneumonia, ViralEarly treatment

Outcome Measures

Primary Outcomes (3)

  • 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

Secondary Outcomes (4)

  • Reduction (change) in GI viral shedding (by PCR)

    Days 0,7,14

  • Change in respiratory viral clearance (by PCR)

    Days 0,7,14

  • Time to resolution of a fever

    Enrolment through final day of participation

  • Negative effects on well being

    Days 0,7,15,28,60

Other Outcomes (1)

  • Incidence of Adverse Events (AEs)

    Enrolment through 30 days after final day of participation

Study Arms (6)

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.

Drug: FluvoxaMINE Maleate 50 MG

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.

Combination Product: Fluvoxamine, Bromhexine

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.

Combination Product: Fluvoxamine, Cyproheptadine

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.

Drug: Niclosamide Pill

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.

Combination Product: Niclosamide, Bromhexine

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.

Interventions

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.

Also known as: Telehealth monitoring
Fluvoxamine Arm
Fluvoxamine, BromhexineCOMBINATION_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.

Also known as: Telehealth monitoring
Fluvoxamine in Combination with Bromhexine Arm
Fluvoxamine, CyproheptadineCOMBINATION_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.

Also known as: Telehealth monitoring
Fluvoxamine in Combination with Cyproheptadine 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. 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.

Also known as: Telehealth monitoring
Niclosamide Arm
Niclosamide, BromhexineCOMBINATION_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.

Also known as: Telehealth monitoring
Niclosamide in Combination with Bromhexine Arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Rajvithi Hospital

Ratchathewi, Bangkok, 10400, Thailand

Location

Vibhavadi Hospital

Bangkok, 10900, Thailand

Location

Chiangmai Neurological Hospital

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

COVID-19Coronavirus InfectionsRespiratory Tract InfectionsPneumonia, Viral

Interventions

FluvoxamineBromhexineCyproheptadineNiclosamide

Condition Hierarchy (Ancestors)

PneumoniaInfectionsVirus DiseasesCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

OximesHydroxylaminesAminesOrganic ChemicalsAniline CompoundsCyclohexylaminesDibenzocycloheptenesBenzocycloheptenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPolycyclic CompoundsSalicylanilidesAnilidesAmidesSalicylamides

Study Officials

  • 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

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Open label, multiarm, prospective, randomised controlled trial
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Fellow and Scientist

Study Record Dates

First Submitted

October 19, 2021

First Posted

October 21, 2021

Study Start

October 1, 2021

Primary Completion

June 21, 2022

Study Completion

June 21, 2022

Last Updated

November 4, 2022

Record last verified: 2022-11

Data Sharing

IPD Sharing
Will not share

Locations