Ivermectin Treatment Efficacy in Covid-19 High Risk Patients
Condition: COVID-19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a multicenter study, which is aimed to investigate the efficacy of the Ivermectin
      drug in high risk COVID-19 patients. This study will compare Ivermectin treatment efficacy
      with standard of care alone. Target cohort is mild to moderate symptomatic Covid-19 (Stage
      2-3), high risk patients aged 50 years and above with comorbidity, who presented to hospitals
      within first 7 days of illness.
    

Detailed description: 
      Objectives

      Primary Objective:

      To assess the effectiveness of Ivermectin in preventing progression of Covid-19 to severe
      disease (clinical stage 4 or 5), which is defined as severe pneumonia requiring oxygen
      supplement or critically ill requiring intensive care.

      Secondary Objectives:

        1. To assess the efficacy of Ivermectin in reducing mortality rate among high risk COVID-19
           patients.

        2. To compare difference in resolution of symptoms, chest radiograph, laboratory
           investigations, ICU admission, mechanical ventilation and length of hospital stay.

      Methodology Study Type and Design This is a multicenter, open-label, randomized controlled
      clinical trial involving COVID-19 designated hospitals in Malaysia. Patients are randomized
      at ratio of 1:1 to groups receiving ivermectin for 5 days plus standard-of-care versus
      standard-of-care only. Patients will be assigned to stratified randomized treatments based on
      a central, computer-generated randomization scheme coordinated by an independent third party.
      Based on national guidelines, all high risk COVID-19 patients will be admitted to hospitals,
      and allow discharge once criteria are met.

      Rationale of ivermectin dose and duration in this study:

      The dose regimens used in various randomized control trials with positive results range from
      0.2mg/kg single dose to 0.6mg/kg/day for 5 days 10-15. PK/PD studies have shown that the
      antiviral effect of Ivermectin is dose dependent 9,15. As SARS-CoV-2 viral load peaks during
      the first week of illness and may prolong in severe disease 18, we believe a high dose of
      ivermectin 0.4mg/kg/day for 5 days would be reasonable and safe to achieve our study
      objectives.

      Standard of care:

      Based on the current Malaysian guidelines, standard of care for mild to moderate Covid-19
      patients includes isolation, infection control, close monitoring (clinical findings,
      laboratory tests, chest imaging) and symptomatic treatment.

      Study Population The population for this clinical trial will be comprised of adults with a
      polymerase chain reaction (PCR) confirmed diagnosis of COVID-19 admitted to any of the
      participating hospitals. Participants who

        1. Treatment group: Ivermectin 0.4mg/kg/day for 5 days + standard-of-care

        2. Control group: Standard-of-care only

      Patients who fulfil the inclusion criteria and do not meet the exclusion criteria will be
      enrolled. Identification of eligible participants will be done prospectively at each study
      site.

      Sample Size Sample size calculation was performed using ScalexProp Version 1.0.2 (Naing,
      2016). The calculation is based on superiority trial design and the primary outcome measure
      of the need to have supplemental oxygen therapy during the hospital admission. We regard a 9%
      difference between intervention arm and control arm as a clinically important outcome. Based
      on local data, 17.5% of COVID-19 aged 50 years and above, with stage 2 and 3 disease and
      comorbidity, progressed to severe disease 3. The need of supplemental oxygen therapy is
      expected to be about 8.8% in intervention arm and 17.5% in control arm. With a margin of
      superiority set to be 1%, the study requires 231 patients for each arm or in total 462
      patients. Considering potential dropouts during the trial, we would require up to 500
      patients or 250 patients each arm. The sample size provides a level of significance at 5%
      with 80% power (2-sided test).
    

Intervention name(s): Ivermectin 0.4mg/kg/day for 5 days
Intervention type(s): Drug
Intervention description(s): Ivermectin 0.4mg/kg/day for 5 days with standard-of-care
Intervention MeSH terms: Ivermectin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a multicenter, open-label, randomized controlled clinical trial involving COVID-19 designated hospitals in Malaysia. Patients are randomized at ratio of 1:1 to groups receiving ivermectin for 5 days plus standard-of-care versus standard-of-care only. Patients will be assigned to stratified randomized treatments based on a central, computer-generated randomization scheme coordinated by an independent third party. Based on national guidelines, all high risk COVID-19 patients will be admitted to hospitals, and allow discharge once criteria met
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Ivermectin; COVID-19