Efficacy of Combination Therapy of Fluvoxamine and Favipiravir versus Favipiravir Monotherapy to Prevent Severe COVID-19 among Mild to Moderate COVID-19 Patients: Open-label Randomized Controlled Trial

Phase 2

Completed

• Conditions: confirmed cases of COVID-19 from SARS-CoV-2 PCR; fluvoxamine, COVID-19, SARS-CoV-2, favipiravir

• Registration Number: TCTR20210615002
• Lead Sponsor: Chulabhorn Royal Academy

Brief Summary

The combined fluvoxamine treatment did not add benefit in preventing deterioration in mild-to-moderate COVID-19 patients without the immunomodulatory effect observed, although it demonstrated low hospitalization rates, oxygen supplemental, intensive care needed, and zero mortality.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-06-15
• Study Completion: 2022-02-22
• Results First Posted: 2023-06-29
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 296

Inclusion Criteria

1) Thai people with age equal or more than 18-year-old
2) Confirmed COVID-19 with 1 or more of the following symptoms; fever, runny nose, cough, myalgia, sore throat, dyspnea, chest discomfort, or chest pain within 7 days after onset of illness
3) Asymptomatic COVID-19
4) Accept to perform chest CT
5) Communicable with staff in Thai
6) Accept the follow-up schedule
7) Nasopharyngeal swab or oropharyngeal swab detected ORF1 a/b gene E gene from SARS-CoV-2 PCR with Ct value less than 35
8) No meet WHO criteria for hospitalization
9) Accept the informed consent

Exclusion Criteria

1)Respiratory tract symptoms compatible with a bacterial infection
2)Previous receiving anti-SARS-CoV-2 agents; an example of favipiravir, remdisevir, protease inhibitors within 24 hours
3)Complete coronavirus vaccination more than 2 weeks
4)History of favipiravir or fluvoxamine allergy
5)Need oxygen therapy
6)Previous use of immunosuppressive agents within 6 months; a corticosteroid, azathioprine, mycophenolate mofetil, cyclosporin, JAK inhibitor
7)Cannot home quarantine
8)Unable to receive enteral nutrition
9)Dyspnea or oxygen desaturation less than 95 on the initial day
10)Respiratory rate more than 30 per minute or BP less than 90/60 or alteration of consciousness (GCS less than 15)
11)Exercise-induced desaturation more than 3%
12)Multiorgan failure or respiratory failure
13)Chest CT presented infiltration of more than 50% of total lung volume (including pure GGOs) or presence of consolidation, crazy paving pattern, or ARDS pattern
14)Severe illness or critical illness followed Gandhi severity score
15)CURB-65 score more than 2, Pneumonia Severity Index more than 90
16)WHO clinical progression scale more than 5 or Brescia-COVID Respiratory Severity Scale (BCRSS) more than 2, or COVID-19 Severity Index more than 8, Quick COVID-19 Severity Index (qCSI) less than 1
17)Modified Centor score more than 2
18)Pregnancy or breastfeeding
19)Terminal illness; end-stage COPD, heart failure, end-stage renal disease, cirrhosis child C
20)Taking medication that had drug interaction with fluvoxamine
20.1) CYP1A2 substrate: agomelatine, tizanidine, aminophylline, theophylline, clozapine, caffeine, melatonin, propranolol
20.2) CYP2C19substrate
- cilostazol, melatonin
- fosphenytoin, phenytoin, voriconazole
- clopidogrel
- serotonergic drugs
- linezolid, rasagiline, selegiline
- antidepressants ex. sertraline, mirtazapine, amitriptyline
- triptans and ergots derivertives; sumatriptan, ergotamine
- lithium
- opioids; morphine, tramadol
- thioridazine
- warfarin
- alprazolam, diazepam
- cyproheptadine
21)Taking the antibiotics, anti-inflammatory drug, NSAIDs, or herb within 48 hours
22)Depression or suicidal idea
23) Glaucoma
24) Receiving chemotherapy
25) Organ transplantation
26)Evidence of any respiratory viral infection other than coronavirus

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Clinical deterioration in mild COVID-19 day 5 VAS score,Clinical deterioration in moderate COVID-19 (pneumonia) day 5 VAS score

Secondary Outcome Measures

Name	Time	Method
Duration from initial treatment to clinical deterioration along study days,the changing of inflammatory marker day 0, 2, 5, 14 laboratory data,Resolution or progression of pneumonia from chest CT or chest X-ray day 5 resolution/ progression,Changing of virological end-point Day 0, 5 ,14 Ct value,Change in GAD-7 and PHQ-9 day 0, 7, 14 GAD-7, PHQ-9,Adverse events anytime descriptive of grading of AE reports,Seroprevalence Day 0, 14 nucleocapsid antibodM, IgGy Ig