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Ivermectin Reproposing for Mild Stage COVID-19 Outpatients

Phase 1
Completed
Conditions
Covid19
SARS (Severe Acute Respiratory Syndrome)
Interventions
Registration Number
NCT04784481
Lead Sponsor
Ministry of Public Health, Argentina
Brief Summary

Background:

The emergency of COVID-19, along with the current difficulties in responding to the high demand for vaccines, requests to the scientific community to find alternative treatments based on reuse of drugs as a strategy to prevent the progression of the disease in patients infected with SARS COV 2.

Objetive This study aims to evaluate the use of ivermectin in mild-stage patients to increase outpatient discharge and prevent the progression to moderate or severe stages of the disease.

Added value of this study We found that an intervention with ivermectin has impacted on the PPS in a population of outpatients care, between the 5th and 9th day. Also, the treatment increased the probability to obtain outpatient discharge, even in the presence of comorbidities.

Implications of all available evidence.

Research in Context According to the COVID-19 Treatment Guidelines by the NIH, most trials have several limitations. It needs results from adequately powered and well-designed clinical trials to provide evidence-based guidance on the role of ivermectin in the treatment of COVID- 19. However, our study shows overlaps in benefits with other authors, and taking together, these results are encouraging for further study about repurposing ivermectin for the treatment of COVID-19.

Detailed Description

Technical Design:

Cluster Randomised Trials in outpatients care, n = 254. The subjects were divided into experimental (EG: n = 110) and control groups (CG: n = 144). The criteria for this choice were based on the geographical distribution of Health Services, locomotion, and logistics in current times of pandemic.

Sample Size:

Sample size was determined by the test comparing two proportions. It considered the following parameters to the bilateral test: n = 30,000 Total operating area population for services network to Primary Care; 95% confidence level, 3% precision, 5% proportion, n = 201 sample size without loss, 20% expected proportion of losses. The sample size calculated was n= 252 participants.

Participants:

The total group n = 254 enrolled outpatients care from the urban area-department heads and peri-urban area of the City San Miguel de Tucumán. The study was conducted between September 2020 to January 2021. The health coverage service was administered by the Health System of the State of Tucumán (SI.PRO.SA, Tucumán, Argentina). 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 054/2020).

Intervention Protocol:

The EG received protocol ivermectin orally 4 tablets of 6 mg = 24 mg every 7 days for 4 weeks plus symptomatic treatment (500mg paracetamol every 6 or 8h, no more than 4 tablets daily;100mg aspirin, 1 tablet per day with breakfast; 150mg Ranitidine, 1 tablet in the morning, and 1 tablet at night). The CG received only symptomatic treatment. Patients with comorbidities continued with the basic medication for the underlying pathology . All participants were evaluated by physical examination and COVID-19 infection was diagnosed with positive RT-PCR. Clinical evaluation of symptoms was carried throughout the study period. Enrolled subjects completed symptom questionnaires (including reporting of any adverse effects of treatment), physical examinations and remote clinical telemedicine follow-up and received outpatient discharge 4 weeks after the start of the intervention.

The 10-category ordinal scale recommended by the WHO was used to classify patients according to clinical patient state: ambulatory mild disease, moderate disease, severe disease.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
254
Inclusion Criteria
  • Outpatients infected by SARSCoV-2 confirmed either by RT-PCR test, Neo Kit or rapid test authorized by ANMAT or by close contact or epidemiological link;
  • Women of childbearing age with a negative pregnancy test;
  • Mild disease-patients with two or more of the following symptoms: fever less than 38·5°C and higher than 37.5°C according to Ministry of Health, Argentina(16), isolated diarrheal episodes, hyposmia or hypogeusia, mild desaturation (between 96 and 93%), dyspnea, polyarthralgia, persistent headache, abdominal pain, erythema of the kidney, nonspecific rash.
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Exclusion Criteria
  • Hypersensitivity or allergy to Ivermectin;
  • Pregnant or lactating;
  • Children or adolescents under 18 years of age;
  • Patients with Neurological Pathology, Renal Insufficiency, Hepatic Insufficiency;
  • Weight less than 40kg;
  • Patients with concomitant use of drugs that act on GABA, barbiturate and benzodiazepine receptors;
  • Patients who have not completed / signed the informed consent.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Experimental GroupIvermectinThe EG received Ivermectin orally 4 tablets of 6 mg = 24 mg every 7 days for 4 weeks. All participants were evaluated by physical examination COVID-19 diagnosed with positive RT-PCR at the beginning, and final of the protocol
Primary Outcome Measures
NameTimeMethod
Proportion testfrom 10th to 14th day.

Proportion of patientts with symptoms (fever, diarrhea, taste and/or smell disturbance, SpO2, polyarthralgia, headache, body pain, abdominal pain, ALRI symptoms and signs)

Secondary Outcome Measures
NameTimeMethod
Odd Ratio28 days after enrollment

Medical release: numbers of participants with absence of clinical symptoms relation to COVID-19 disease.

Odd Ratio and logistic regression test28 days after enrollment

Relative risk of being cured "with" or "without" treatment

Trial Locations

Locations (1)

SI.PRO.SA, Ministerio de Salud Pública

🇦🇷

Tucumán, Argentina

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