Covid-19 living Data

Ivermectin vs Hydroxychloroquine (RCT)

Hospitalized patients

FOREST PLOTS -2021-07-29

Studies description

Trial NCT04391127
Publication Beltran-Gonzalez J, medRxiv (2021) (preprint)
Dates: 2020-05-04 to 2020-08-15
Funding: Public/non profit (Aguascalienes State Health Institute)
Conflict of interest: No

Methods
	RCT Blinding: Double blinded, no restrictions
	Location : Single center / Mexico Follow-up duration (days): 30
Inclusion criteria	Age 16 to 90 years hospitalized positive RT-PCR for SARS-CoV-2 by nasal and oropharyngeal swabbing pneumonia, diagnosed by X-ray or high-resolution chest CT scan, with a pattern suggesting involvement due to coronavirus recently established hypoxemic respiratory failure or acute clinical deterioration of pre-existing lung or heart disease.
Exclusion criteria	Required high oxygen volumes (face mask > 10 L/ min) had predictors of a poor response to high-flow oxygen nasal prong therapy required mechanical ventilation
Interventions
	Treatment Hydroxychloroquine Initial dose: 400 mg orally twice a day for the first day. Maintenance dose: 200 mg orally twice a day for another 4 days. Ivermectin 12 mg for one day in patients weighing < 80 kg and 18 mg for one day in those >80 kg.
	Control Placebo Two calcium citrate tablets orally twice a day for one day. Subsequently one tablet twice a day for 4 more days.
Participants
	Randomized participants : Hydroxychloroquine=33 Ivermectin=36 Placebo=37
	Characteristics of participants N= 106 Mean age : NR 66 males Severity : Mild: n=0 / Moderate: n=16 / Severe: n=90 Critical: n=0
Primary outcome
	In the register Mean days of hospital stay [ Time Frame: Three months ]; Rate of Respiratory deterioration, requirement of invasive mechanical ventilation or dead [ Time Frame: Three months ]; Mean of oxygenation index delta [ Time Frame: Three months ]
	In the report Hospitalization duration until discharge due to clinical improvement, the total duration of hospitalization, and the safety outcomes were duration of hospitalization until respiratory deterioration (previously defined) or death
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the trial registry was used in data extraction and assessment of risk of bias. Neither study protocol nor statistical analysis plan was available. Inclusion criteria in registry and the pre-print article differ slightly in that the pre-print article also included hypoxemic respiratory failure or acute clinical deterioration of pre-existing lung or heart disease. Some pre-stated primary (i.e., mean of oxygenation index delta) and secondary (i.e., mean time to negative PCR) outcomes were not reported. There were no substantive differences between the pre-print article and the trial registry in interventions. Patients considered at high risk of development of QT interval prolongation due to hydroxychloroquine were only randomized to the ivermectin or placebo arms. The trial was terminated due to a reduction in eligible participants. As a result, the target sample size was not achieved. This trial was updated on July 28th, 2021 with data gained from contact with authors.

Trial RBR-8h7q82
Publication Galan L , Pathog Glob Health (2021) (published paper)

Funding: Public/non profit (Universidade Federal de Roraima)
Conflict of interest: No

Methods
	RCT Blinding: Participants, outcome assessor and health care pro
	Location : Single center / Brazil Follow-up duration (days): 90
Inclusion criteria	Laboratory test confirming infection by SARS-CoV-2 (positive serologic test IgM or rt-PCR) hospitalized with a clinical, epidemiological, and radiological picture compatible with COVID-19 over 18 years old present a severe form of the disease characterized by one of the following clinical signs: dyspnea, tachypnea (>30 bpm), peripheral oxygen saturation <93% (pulse oximeter evaluation), PaO2/FiO2 ratio <300, or infiltrate pulmonary>50% of the parenchyma seen on chest tomography or chest radiography.
Exclusion criteria	Under 18 years old indigenous people patients not fluent in Portuguese unable to understand the objectives and methods of the study critically ill patients who are not accompanied by legal representatives those who reject participation in the study patients with cardiac arrhythmia that include prolongation of the QT interval previous use of any of the medications surveyed for more than 24 h.
Interventions
	Treatment Hydroxychloroquine Initial dose: 400 mg orally twice on day 0 - Maintenance dose: 400 mg orally once daily twice on day 1, and once daily from day 2 to day 5 Chloroquine Initial dose: 450 mg orally twice on day 0 -Maintenance dose: 450 mg orally twice on day 1, and once daily from day 2 to day 5
	Control Ivermectin 14 mg orally once from day 1 to day 3 (+ placebo tablets on days 1, 4 & 5 to maintain blinding)
Participants
	Randomized participants : Hydroxychloroquine=54 Chloroquine=61 Ivermectin=53
	Characteristics of participants N= 168 Mean age : NR 95 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=*
Primary outcome
	In the register Need for supplemental oxygen, need for invasive ventilation, need for admission to the intensive care unit (ICU)
	In the report Overall survival
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	*
General comment	The prospective trial registry was available. There were no differences between the published article and the registry in population or interventions. The study achieved its target sample size. No study protocol or statistical analysis plan was available. Outcomes reported were no relevant for the COVID-19 NMA. Consequently, no outcome data have been extracted for this study.