Cochrane COVID-19 Study Register
NCT04341493

Treatment With Hydroxychloroquine vs Nitazoxanide + Hydroxychloroquine in Patients With COVID-19 With Risk Factors for Poor Outcome

  1. Study Type
  2. Interventional
  1. Study Aim
  2. Treatment and Management
  1. Study Design
  2. Parallel/Crossover
  1. Intervention Assignment
  2. Randomised
  1. Population (9)
  2. Male and Female
  3. COVID-19
  4. Adult
  5. Aged (65+)
  6. Child
  1. Intervention (2)
  2. Hydroxychloroquine
  3. Nitazoxanide
  1. Comparison (1)
  2. Hydroxychloroquine
  1. Outcome (1)
  2. Mechanical ventilation

Hydroxychloroquine vs Nitazoxanide in Patients With COVID-19

Hugo Mendieta Zeron
First Published (first received 2020 Apr 10)ClinicalTrials.gov (https://clinicaltrials.gov/show/NCT04341493)
Trial registry record
No Results
Introduction The current pandemic caused by the SARS-COV2 coronavirus (COVID-19) is life-threatening and is challenging the world's best health systems. Accelerated spread of this pandemia led physicians to try a variety of treatments without a well established sequence due to ignorance about this new disease. The case fatality rate has been calculated at 2.2% but there are differences depending on the country affected. Perspective When comparing the evolution of cases between Spain and Mexico, an apparently less pronounced trend is observed in Mexico, but this may be due to underdiagnosis. In calculations by the Mexican Ministry of Health, around 6% of the patients (approximately 10,500) who contract COVID-19 could be found serious and in need of hospitalization in intensive care. NTZx NTZx and its circulating active metabolite, tizoxanide, inhibit the replication of a wide range of viruses, both RNA and DNA. It has action against 16 strains of Influenza A virus subtypes H1N1, H3N2, H3N2v, H3N8, H5N9, H7N1 and a strain of influenza B. It also works against respiratory syncytial virus, norovirus, dengue, yellow fever, Japanese encephalitis virus, rotavirus , hepatitis B and C, even against the human immunodeficiency virus (Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS). Problem Mexico is in Phase 2 according to the World Health Organization (WHO) and more local infections due to coronaviruses are expected. To date, various COVID-19 treatment schemes are being tested, but the usefulness of none can be assured. When reviewing the drug schemes that are being carried out in the world, it calls the attention that developing countries are not included, beyond the fact that the tested alternatives are economically inaccessible. This clinical survey aims to test the possible utility of NTZx against COVID-19, alone or in combination with hydroxychloroquine

Treatment with hydroxychloroquine vs hydroxychloroquine + nitazoxanide in COVID-19 patients with risk factors for poor prognosis: a structured summary of a study protocol for a randomised controlled trial

Calderon JM, Zeron HM, Padmanabhan S
Journal article
No Results
OBJECTIVES: To determine the efficacy of Hydroxychloroquine vs. Hydroxychloroquine + Nitazoxanide in reducing the need for invasive mechanical ventilatory support for patients with COVID-19. Hydroxychloroquine is currently being used in multiple trials with varying doses in an attempt to treat COVID-19. Nitazoxanide has powerful antiviral effects and proven efficacy against a range of viruses including SARS and MERS. Dual therapy by combining appropriate doses of these two medications with diverse activities against COVID-19 is expected to be better than monotherapy with hydroxychloroquine. TRIAL DESIGN: This is a single centre, randomized, controlled, single blinded, 2 arm (ratio 1:1) parallel group trial. PARTICIPANTS: 86 COVID-19 positive patients that are being treated at the Health Institute of the State of Mexico (ISEM) in Toluca, State of Mexico will be recruited from May 14 to December 31, 2020. INCLUSION CRITERIA: 1)Age older than 18 years.2)Hospitalised COVID-19 PCR test positive patients.3)Within the first 72 hours after performing the PCR test.4)Presence of risk factors for complications (at least one): over 60 years, history of diabetes mellitus, hypertension, and morbid obesity. EXCLUSION CRITERIA: 1)Patients with corrected QT interval (QTc) greater than 500ms at hospital admission.2)Patients who have inherent contraindications to each drug.3)Patients who are unable to consent.4)Patients who have previously received chloroquine.5)Patients already intubated. Elimination criteria: 1)Patients whose clinical follow-up is lost or who decide not to continue in the study INTERVENTION AND COMPARATOR: The two management alternatives will be: Control - Hydroxychloroquine 200 mg taken orally every 12 hours for 7 days. Dual therapy - Hydroxychloroquine 400 mg taken orally every 12 hours for two days and then 200 mg taken orally every 12 hours for four days + Nitazoxanide 500 mg orally every 6 hours taken with food, for seven days. MAIN OUTCOMES: Primary: Mechanical ventilation requirement assessed at one week. Percentage of COVID-19 positive patients who require mechanical ventilation . All patients will be monitored till hospital discharge or death. RANDOMISATION: Patients will be randomly allocated using allocation papers and opaque sealed envelopes to either receive the placebo or the dual therapy intervention treatment in a 1:1 ratio until we have recruited the required number of patients for each group. BLINDING (MASKING): Trial participants will be blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 86 participants will be randomized to each group, with 43 in the control group and 43 in the dual therapy group. TRIAL STATUS: Protocol version: 2, recruitment will begin on May 14 until sample size is reached , with the analysis deadline of December 31st 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04341493. Date of trial registration: April 10, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol