A RANDOMIZED TRIAL - INTENSIVE TREATMENT BASED IN IVERMECTIN AND IOTA-CARRAGEENAN AS PRE-EXPOSURE PROPHYLAXIS FOR COVID- 19 IN HEALTHCARE AGENTS

  1. Rossana Elena Chahla
  2. Luis Medina Ruiz
  3. Eugenia Silvana Ortega
  4. Marcelo Fabio Morales
  5. Francisco Barreiro
  6. Alexia George
  7. Cesar Mancilla
  8. Sylvia Paola D’ Amato
  9. Guillermo Barrenechea
  10. Daniel Gustavo Goroso
  11. Maria de los Angeles Peral de Bruno

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Abstract

IMPORTANCE

The emergency of COVID-19 requires the implementation of urgent strategies to prevent the spread of the disease, mainly in health personnel, who are the most exposed and has the highest risk of becoming infected with the SARS-COV-2. Drug repurposing is a pragmatic strategy, a faster and cheaper option, compared to the new drug development that has proven successful for many drugs and can be a key tool in emergency situations such as the current one that requires quick action. In addition, considering the limited access to vaccines for developing countries, preventive use of ivermectin can be a palliative that minimizes the risks of infection.

OBJECTIVE

To evaluate the protective effect of the combination Ivermectin / Iota-Carrageenan (IVER/IOTACRC), intensive treatment with repeated administration in oral- and nasal-spray, respectively, as a prophylaxis treatment prior to exposure to SARS-CoV-2, in health personnel at Public Healthcare Centers.

PARTICIPANTS, DESIGN AND SETTING

Randomized controlled 1-1 clinical trial in Personal Health, n = 234. The subjects were divided into experimental (EG: n=117; 39.6 ± 9.4 years old, 65F) and control groups (CG: n=117; 38.4 ± 7.4 years old, 61F). The EG received Ivermectin orally 2 tablets of 6 mg = 12 mg every 7 days, and Iota-Carrageenan 6 sprays per day for 4 weeks. All participants were evaluated by physical examination COVID-19 diagnosed with negative RT-PCR at the beginning, final, and follow-up of the protocol. Differences between the variables were determined using the Chi-square test. The proportion test almost contagious subject and the contagion risk (Odds Ratio) were calculated using software STATA. The level of statistical significance was reached when p-Value < 0.05.

RESULT

The number of subjects who were diagnosed with COVID-19 in EG was lower, only 4 of 117 (3.4%) than subjects in CG: 25 of 117 (21.4%) ( P-Value = 1.10 −5 ). Nineteen patients had mild symptoms, 4 were in EG whereas, 15 were in CG ( p -Value = 0.001). Seven subjects were moderate, and 3 with severe diagnostics, all them in CG. The probability (Odds Ratio) of becoming ill with COVID-19 was significantly lower in EG with values of 0.13, 95% 0.03 to 0.40; p -Value = 1.10 −4 , this value (<1) indicates a protective effect of the IVER/IOTACRC in the EG. Logistic regression test demonstrated that treatment was effective to prevent COVID-19 (Odds Ratio 0.11, 95% 0.03 to 0.33; p -Value = 1.10 −4 ). We also found that when increase the age, decrease contagious risk (Odds Ratio 0, 93, 95% 0.88 to 0.98, p -Value= 0, 02). On the other hand, the probability of contracting COVID-19 was dependent on the patient’s preexisting comorbidity (Odds Ratio 5.58, 95% 2.20 to 14.16, p -Value = 1.10 −5 ). The other variables sex and designation were independent.

CONCLUSION

The intensive preventive treatment (short-term) with IVER/IOTACRC was able to reduce the number of health workers infected with COVID-19. This treatment had also effect in preventing the severity of the disease, since all patients treated were mild. We propose a new therapeutic alternative for prevention and short-term intervention scheme (intensive) that is of benefit of the health worker in this pandemic accelerated time. This intervention did not produce lack of adherence to treatment or adverse effects.

Trial Registration

ClinicalTrials.gov Identifier: NCT04701710

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  1. ScreenIT

    SciScore for 10.1101/2021.03.26.21254398: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: The people who agreed to participate in the study gave their informed consent before starting the study (Research Ethics Committee / Health Research Directorate, file number 52/2020).
    IRB: The people who agreed to participate in the study gave their informed consent before starting the study (Research Ethics Committee / Health Research Directorate, file number 52/2020).
    RandomizationThen, 117 of them were randomly selected to generate the CG and EG.
    Blindingnot detected.
    Power AnalysisIt were considerate the following parameters to bilateral test: 95% confidence level, 95% statistical power, 95% proportion of infected patients in the CG, 85% proportion of infected patients in the EG.
    Sex as a biological variableThe exclusion criteria were people under 18 years of age, pregnant or actively breastfeeding women, presenting symptoms related to COVID-19 disease, concurrent autoimmune or chronic disease, immune suppression, active infectious diseases, a history of previous SARS-CoV-2 infection confirmed by RT-PCR, medical history, and a clinical questioning.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Intervention Protocol: The individuals of the EG received active treatment with IVER/IOTACRC.
    IVER/IOTACRC
    suggested: None
    Calculations were performed using STATA 11.2.
    STATA
    suggested: (Stata, RRID:SCR_012763)

    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: We detected the following sentences addressing limitations in the study:
    It is more relevant considering the limitations in vaccines supplies. Limitations: The main limitation of this study was the number of agents to enroll. This trial does not include the report of adverse event in the long run, so will be interesting to include in future trials biochemical examination for control of potential adverse effects. Financial limitations impacted in the study design, which not involved blinded evaluation and/or placebo administration. It’s also for considering the limitations of RT-PCR test in relation to diagnosis, which in future works can be complimented with other approved qualitative tests. On this last point, economic constraints had a determining rol. Future work: We consider that our results, taking together with other trials, are encouraging for develop further studies. New clinical intervention studies in our region and also partners in other countries that may show the effect of the IVER/IOTACRC compound in mildstage outpatients. The design that would be proposed would be to use the same treatment time but at higher doses. Other way, more strong results could be obtained from randomized double blinded studies with long term controls to arrive to solid conclusions about safety and efficacy of IVER/IOTACRC

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

    IdentifierStatusTitle
    NCT04701710CompletedProphylaxis Covid-19 in Healthcare Agents by Intensive Treat…

    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

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  2. Version published to 10.1101/2021.03.26.21254398v1 on medRxiv