Trial NCT04405843
Publication Lopez-Medina E, JAMA (2021) (published paper)
Dates: 2020-07-15 to 2020-11-30
Funding: Mixed (Centro de Estudios en Infectologia Pediatrica; Tecnoquimicas (drug and placebo donation))
Conflict of interest: Yes

Methods
RCT
Blinding: Participants, outcome assessor and health care pro
Location : Single center / Colombia
Follow-up duration (days): 21
Inclusion criteria
  • 1) Adult men and non–pregnant or breast-feeding women over 18 years of age

  • 2) SARS CoV2 / COVID 19 disease confirmed by RT-PCR in any of the laboratories that report to the Departmental Health Secretary, approved for the diagnosis of COVID-19 by the National Institute of Health

  • 3) Onset of symptoms began within the previous 7 days and they had mild disease, defined as being at home or hospitalized but not receiving high-flow nasal oxygen or mechanical ventilation (invasive or noninvasive).
Exclusion criteria
  • 1) Medical history of liver disease

  • 2) History of allergy to ivermectin or any of its components

  • 3) Belonging to another clinical trial that evaluates the efficacy of an investigational drug against COVID-19. The use of other treatments outside of clinical trials is allowed

  • 4) Patients who were asymptomatic

  • 5) Had severe pneumonia

  • 6) Had received ivermectin within the previous 5 days

  • 7) Subjects receiving Warfarin, erdafitinib, or quinidine

  • 8) Had hepatic dysfunction or liver function test results more than 1.5 times the normal level.
Interventions
Treatment
Ivermectin
300 mcg/kg/day orally for 5 days
Control
Placebo

Participants
Randomized
participants :
Ivermectin=238
Placebo=238
Characteristics of participants
N= 476
Mean age : NR
167 males
Severity : Mild: n= 394/ Asymptomatic: n=0
Number of vaccinated participants: NR
Primary outcome
In the register
Time until resolution of symptoms [ Time Frame: 21 days ]
In the report
Time from randomization to complete resolution of symptoms within the 21-day follow-up period
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

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 published article, the study protocol, statistical analysis plan and trial registry were used in data extraction and assessment of risk of bias. The original primary outcome measure (worsening by 2 points in an 8-point ordinal scale) was changed to resolution of symptoms during the trial due to low incidence of the original outcome, resulting an unattainable sample size. This change was identified before the interim analysis and approved by the data and safety monitoring board.
Other than that there were no substantive differences between the published article and the study protocol, statistical analysis plan and trial registry.
For two weeks both arms received Ivermectin due to a labeling error, including 38 in the control group; all patients recruited during this period (n=75) were not included in primary analyses extracted here, but were included in sensitivity and as-treated analysis.
Quote: "On October 20, 2020, the lead pharmacist observed that a labeling error had occurred between September 29 and October 15, 2020, resulting in all patients receiving ivermectin and none receiving placebo during this time frame. The study blind was not unmasked due to this error. The data and safety monitoring board recommended excluding these patients from the primary analysis but retaining them for sensitivity analysis. The protocol was amended to replace these patients to retain the originally calculated study power. The primary analysis population included patients who were analyzed according to their randomization group, but excluded patients recruited between September 29 and October 15, 2020, as well as patients who were randomized but later found to be in violation of selection criteria. Patients were analyzed according to the treatment they received in the as-treated population (sensitivity analysis)."
This study was updated on May 19th, 2021 with data gained from contact with authors.