Covid-19 living Data

Enisamium vs Placebo (RCT)

Hospitalized patients

FOREST PLOTS -2022-12-06

Studies description

Trial NCT04682873
Publication Holubovska O, medRxiv (2022) (preprint)
Dates: 2020-05-15 to 2021-03-26
Funding: Mixed (Farmak. A.T.V. is supported by joint Wellcome Trust and Royal Society grant 206579/Z/17/Z)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Ukraine Follow-up duration (days): 29
Inclusion criteria	Willing and able to provide written informed consent Aged ≥ 18 years SARS-CoV-2 infection confirmed by PCR ≤ 4 days before randomization Currently hospitalized due to SARS-CoV-2 infection with fever, defined as body temperature ≥ 37.8 °C Modified World Health Organization (WHO) Ordinal Scale for Clinical Status Patient state in Covid-19: score 4 i.e. hospitalized, virus-positive, oxygen by mask or nasal prongs.
Exclusion criteria	Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited < 24 hours prior to start of IMP treatment Requiring mechanical ventilation at screening or it is expected within 24 h after inclusion Expected survival time < 72 hours for any reason Positive pregnancy test Breastfeeding woman Presence of renal dysfunction defined as estimated glomerular filtration rate (eGFR) <60 mL/min, total bilirubin ≥ 2.0 mg/dL, Thyroid stimulating hormone (TSH) outside normal range and / or Aspartate aminotransferase (ASAT)/ Alanine aminotransferase (ALAT) above threefold upper limit of normal range (known from patients medical history) Known hypersensitivity to the trial drug, the metabolites, or formulation excipient History or presence of drug or alcohol abuse History or presence of diseases of thyroid gland Parallel participation in another clinical trial with an investigational product, participation in a clinical trial within less than 6 weeks prior to visit 1 Known to be, or suspected of being unable to comply with the trial protocol (e.g., no permanent address, history of drug abuse, known to be non-compliant or presenting an unstable psychiatric history) Legal incapacity and / or other circumstances render the subject unable to understand the trial's nature, scope and possible impact Subject in custody by juridical or official order Subject who has difficulties in understanding the language (Ukrainian) in which the subject information (informed consent form) is given Subjects who are members of the staff of the trial center, staff of the sponsor or the clinical research organisation (CRO), the investigator him- / herself or close relatives of the investigator.
Interventions
	Treatment Enisamium 500 mg every 6 hours for 168 hours
	Control Placebo
Participants
	Randomized participants : Placebo=296 Enisamium=296
	Characteristics of participants N= 592 Mean age : NR 134 males Severity : Mild: n=0 / Moderate: n=285 / Severe: n=0 Critical: n=0
Primary outcome
	In the register Time from day of randomization to an increase of at least two points (from the status at randomization) on the following severity rating (SR) scale in days [Time Frame: Day 0 to Day 29]: 1 Death; 2 Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3 Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4 Hospitalized, requiring supplemental oxygen; 5 Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (Covid-19 related or otherwise); 6 Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7 Not hospitalized, limitation on activities and/or requiring home oxygen; 8 Not hospitalized, no limitations on activities
	In the report The time to improvement of the patient's condition by 2 points (from 4 to 6) on the modified WHO scale (Table 1), as measured by assessment of the patient's condition.
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 and supplementary materials were used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. There were substantial differences between the outcomes in the registry and the pre-print article. Interim analysis of an ongoing study. This study was updated on November 30th, 2022 with data extracted from the preprint reporting on final results. This trial initially included patients with a baseline modified WHO severity rating (SR) of 4 and 5, however, "interim data revealed that no relevant treatment difference could be observed in patients with a baseline of SR = 5". Thus, for the final analysis, these patients were excluded.