RCT 60 low-risk outpatients, median age 31, with mild to moderate COVID-19 showing no significant differences with combined favipiravir/ivermectin/niclosamide treatment compared to favipiravir alone. There was limited room for improvement with almost no progression and no hospitalization, ICU admission, supplemental oxygen, or mortality.
The combined group showed significantly improved visual analog scale (VAS) scores for cough, runny nose, and diarrhea from day 3.
Authors note that "the WHO-CPS were significantly decreased among FPV/IVM/NCL vs FPV alone on day 10", however the degree of improvement cannot be determined based on the values reported.
Authors state that "All data generated or analyzed during this study are included in this published article", which is incorrect - only summary statistics are published. The trial registration states that data will not be made available. This raises concerns, especially given many inconsistencies in the published data:
- E gene and ORF1 a/b gene day 1 Ct values are different between Table S1 and Table S3.
- Figure S1 shows 25% >= 38.5, however no number of 30 patients is 25%, and this does not match Table 2 (at most 23.3% >= 38.5).
- The first three calculations in section 3.3 all show p = 0.515, an unusual match for different calculations.
- "the FPV/IVM/NCL group had 0.62 cycles per day fewer than did the FPV group" does not match the data.
- Table 1 shows 30% loss of taste in the control group, however Table S2 shows a Q3 VAS score of 0, which is inconsistent.
- The abstract reference to significant differences for sore throat does not match the results in Table S6.
Not releasing data is a change from earlier COVID-19 trials by the same main author: TCTR20210615002 and TCTR20210609001 both indicate that individual patient level data would be available.
The trial was registered retrospectively. Discussion of prior research is very biased, however this may be required for publication. There were more patients with fever, anosmia, and loss of taste at baseline in the combined group. The adverse events reported show none of the expected side effects of ivermectin at the dose used.
This study is excluded in the after exclusion results of meta
analysis:
data consistency issues, very low risk patients/variants with almost no progression, all patients received known effective antiviral, baseline differences.
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risk of progression, no change, RR 1.00, p = 1.00, treatment 1 of 30 (3.3%), control 1 of 30 (3.3%), chest xray progression, day 6.
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risk of progression, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 30 (0.0%), control 1 of 30 (3.3%), NNT 30, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), chest xray progression, day 3.
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risk of no recovery, 39.4% lower, RR 0.61, p = 0.19, treatment 30, control 30, combined symptoms.
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risk of no recovery, 70.0% lower, RR 0.30, p = 0.048, treatment 30, control 30, mid-recovery, day 3, cough.
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risk of no recovery, 14.3% lower, RR 0.86, p = 0.38, treatment 30, control 30, mid-recovery, day 3, sore throat.
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risk of no recovery, 66.7% lower, RR 0.33, p = 0.41, treatment 30, control 30, inverted to make RR<1 favor treatment, mid-recovery, day 3, runny nose.
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risk of no recovery, 50.0% lower, RR 0.50, p = 0.32, treatment 30, control 30, inverted to make RR<1 favor treatment, day 6, cough.
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risk of no recovery, no change, RR 1.00, p = 0.61, treatment 30, control 30, WHO-CPS.
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relative Ct improvement, 6.1% better, RR 0.94, p = 0.75, treatment median 9.15 IQR 9.7 n=30, control median 8.59 IQR 8.239999999999995 n=30, E gene, mid-recovery, day 5, primary outcome.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Siripongboonsitti et al., 29 Mar 2024, Randomized Controlled Trial, Thailand, peer-reviewed, 5 authors, study period 7 December, 2022 - 3 February, 2023, dosage 600μg/kg days 1-5, this trial uses multiple treatments in the treatment arm (combined with niclosamide) - results of individual treatments may vary, trial
TCTR20230403007 (FINCOV).
A Randomized Trial to Assess the Acceleration of Viral Clearance by the Combination Favipiravir/Ivermectin/Niclosamide in Mild-to-Moderate COVID-19 Adult Patients (FINCOV)
M.D Taweegrit Siripongboonsitti, Kriangkrai Tawinprai, M.D Panisadee Avirutnan, Ph.D. e Kunlakanya Jitobaom, Prasert Auewarakul
doi:10.1016/j.jiph.2024.03.030
Background: The efficacy of the viral clearance and clinical outcomes of favipiravir (FPV) in outpatients being treated for coronavirus disease 2019 (COVID-19) is unclear. Ivermectin (IVM), niclosamide (NCL), and FPV demonstrated synergistic effects in vitro for exceed 78% inhibiting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) replication. Methods: A phase 2, open-label, 1:1, randomized, controlled trial was conducted on Thai patients with mild-to-moderate COVID-19 who received either combination FPV/IVM/NCL therapy or FPV alone to assess the rate of viral clearance among individuals with mild-to-moderate COVID-19. Results: Sixty non-high-risk comorbid patients with mild-to-moderate COVID-19 were randomized; 30 received FPV/IVM/NCL, and 30 received FPV alone. Mixed-effects multiple linear regression analysis of the cycle threshold value from SARS-CoV-2 PCR demonstrated no statistically significant differences in viral clearance rates between the combined FPV/IVM/NCL therapy group and the FPV-alone group. World Health Organization Clinical Progression scores and symptomatic improvement did not differ between arms on days 3, 6, and 10, and no adverse J o u r n a l P r e -p r o o f events were reported. No patients required hospitalization, intensive care unit admission, or supplemental oxygen or died within 28 days. C-reactive protein on day 3 was lower in the FPV/IVM/NCL group.
Conclusion: Viral clearance rates did not differ significantly between the FPV/IVM/NCL combination therapy and FPV-alone groups of individuals with mild-to-moderate COVID-19, although the combined regimen demonstrated a synergistic effect in vitro. No discernible clinical benefit was observed. Further research is required to explore the potential benefits of FVP beyond its antiviral effects.
Conflicts of Interest The authors declare that they have no competing interests.
J o u r n a l P r e -p r o o f
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