Nitazoxanide vs Standard care/Placebo (RCT)

Hospitalized patients

FOREST PLOTS -2022-01-04

Studies description

Trial NCT04348409
Publication Blum VF, EClinicalMedicine (2021) (published paper)
Dates: 2020-05-20 to 2020-09-21
Funding: Private (Farmoquimica (FQM), Brazil)
Conflict of interest: Yes

Methods
RCT
Blinding: double blinding
Location : Multicenter / Brazil
Follow-up duration (days): 21
Inclusion criteria
  • Diagnosed with COVID-19
  • positive qPCR and compatible symptoms
  • aged 18 years or older, both genders
  • hospitalized in a non-critical condition with mild respiratory insufficiency
  • maximum of 36 hours of symptoms.
Exclusion criteria
  • Patients infected with HIV, HTLV I or II
  • participants in antineoplastic treatment
  • patients with severe autoimmune diseases in immunosuppression
  • transplant recipients, pregnant or lactating women, or any other clinical condition that the Investigator deemed to be an imminent risk to health and participant's life were excluded. Patients who received previous therapies for COVID-19 of any kind were excluded, as well as medications that would be directed against specific manifestations of COVID-19, such as monoclonal antibodies or anti interleukins.
Interventions
Treatment
Nitazoxanide
600 mg orally twice a day for 7 days
Control
Placebo

Participants
Randomized
participants :
Nitazoxanide =25
Placebo=25
Characteristics of participants
N= 50
Mean age : NR
15 males
Severity : Mild: n=* / Moderate: n=* / Severe: n=0 Critical: n=0
Primary outcome
In the register
Viral load [ Time Frame: day 1, 4, 7, 14 and 21 ]
In the report
Virological response to treatment
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 peer-reviewed journal publication and 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. The study achieved its pre-stated sample size. There is no significant difference from the trial registration in the population or intervention and control treatments. The scale used to categorize clinical status differed between the trial registry and the pre-print article, having been adapted to include fewer points for assessment of a small sample. The article reports adverse events and several laboratory outcomes that were not included in the registry. Only proportions were reported for clinical improvement (hospital discharge) with unclear denominators and number of cases. Viral negative conversion was reported, but at a follow-up duration that was too long for the COIVD-19 NMA (21 days); thus it was not included. On 26th of July, 2021, this study was updated based on updated pre-print.
On December 23rd, 2021, this study was updated after publication of a corrigendum.

Trial NCT04463264
Publication Silva M, medRxiv (2021) (preprint)
Dates: 2020-07-01 to 2020-12-30
Funding: Private (Laboratorios Roemmers S.A.I.C.F.)
Conflict of interest: Yes

Methods
RCT
Blinding: Single blinded, no restrictions
Location : Multicenter / Argentina
Follow-up duration (days): 35
Inclusion criteria
  • People of both sexes aged ≥ 18 years with COVID-19
  • a positive quantitative real-time polymerase reaction (rtq-PCR)
  • no more than 4 days after the onset of symptoms.
Exclusion criteria
  • Pregnant or lactating women
  • subjects with any contraindication to the use of NTX (according to its package leaflet).
Interventions
Treatment
Nitazoxanide
500 mg orally 4 times a day for 14 days.
Control
Placebo

Participants
Randomized
participants :
Nitazoxanide =33
Placebo=13
Characteristics of participants
N= 46
Mean age : NR
26 males
Severity : Mild: n=25 / Moderate: n=0 / Severe: n=0 Critical: n=0
Primary outcome
In the register
Eradication of SARS COV-2 from patients' respiratory tract secretions by treatment day 7th. [Time Frame: 7 day]
In the report
Viral eradication from the patients’ respiratory tract secretions on day 7 after starting treatment (a viral eradication of at least 35% would be clinically relevant).
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
High
General comment
In addition to the available version of the pre-print article, the study registry was used in data extraction and risk of bias assessment.
There is no change from the trial registration in the intervention and control treatments.
The authors stated that the original protocol included an interim analysis to find any trends upon enrolment of 1/3 of the proposed number of patients (interim analysis). As a result, the target sample size specified in the registry was not achieved and some efficacy outcomes were not reported in the paper.
In this interim analysis only virological outcomes are reported. Other outcomes in the trial registry such as clinical improvement (WHO scale), hospitalization and mechanical ventilation/ICU requirement are not reported.
The primary and secondary efficacy analyses were performed as per protocol. It includes patients with complete data on days 1 and 7 and who received the indicated treatment (two patients without data on day 7 and one patient randomized to NTX but treated with doses well below the protocol doses were excluded).