Ivermectin shows clinical benefits in mild to moderate COVID19: a randomized controlled double-blind, dose-response study in Lagos

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Abstract

Introduction

In vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS—CoV-2 viral replication, but questions remained as to in-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19.

Methods

We conducted a translational proof of concept randomized, double blind placebo controlled, dose response and parallel group study of IV efficacy in RT—polymerase chain reaction proven COVID 19 positive patients. Sixty-two patients were randomized to three treatment groups. (A) IV 6 mg regime, (B) IV 12 mg regime (given Q84 h for 2 weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care.

Results

The Days to COVID negativity (DTN) was significantly and dose dependently reduced by IV (P = 0.0066). The DTN for Control were, = 9.1+/–5.2, for A 6.0 +/– 2.9 and for B 4.6 +/–3.2. Two way repeated measures ANOVA of ranked COVID 19 +/– scores at 0, 84, 168 and252h showed a significant IV treatment effect (P = 0.035) and time effect (P < 0.0001). IV also tended to increase SPO2% compared to controls, P = 0.073, 95% CI—0.39 to 2.59 and increased platelet count compared to C (P = 0.037) 95%CI 5.55—162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = –0.52, P = 0.005). No SAE was reported.

Conclusions

12mg IV regime given twice a week may have superior efficacy over 6mg IV given twice a week, and certainly over the non IV arm of the study. IV should be considered for use in clinical management of SARS-COV2, and may find applications in prophylaxis in high risk areas.

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  1. SciScore for 10.1101/2021.01.05.21249131: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study protocol received ethical review and approval of the Institutional Review Board of the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria.
    Consent: The patient inclusion criteria were COVID 19 PCR proven positive patients, who gave informed, written consent to participate in the study, and were either asymptomatic or had mild/moderate symptoms.
    RandomizationThe study was a proof of concept (PoC), double blind, randomized controlled trial, of a parallel group, dose-response design.
    BlindingThe study was a proof of concept (PoC), double blind, randomized controlled trial, of a parallel group, dose-response design.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.


    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    ISRCTN40302986NANA


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. SciScore for 10.1101/2021.01.05.21249131: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementThe study protocol received ethical review and approval of the Institutional Review Board of the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria.Randomization62 patients were randomized to 3 treatment groups.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableectin B Number per arm 21 21 Age (years) 48.3 39.7 Male 15 14 Female 6 7 Symptoms Fever 30% 42.8% Headache 50% 57% Cough 30% 19% Dyspnea 20% 23% Signs Anosmia/Ageusi 25% 15% a Resp. rate /min 26(6.2 23.6(6 ) .

    Table 2: Resources

    No key resources detected.


    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.


    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.