Covid-19 Living Data

Trial NCT04324021
Publication Andersson H, Unpublished (2022) (results posted on registry)

Funding: Private (Swedish Orphan Biovitrum)
Conflict of interest: *

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / USA, Italy Follow-up duration (days): 70
Inclusion criteria	Signed informed consent provided by the patient, or by the patient's legally authorized representative(s), as applicable Documented presence of SARS-CoV-2 infection as per hospital routine Age > 18 to < 85 years at the time of screening Presence of respiratory distress, defined as: PaO2/FiO2 < 300 mm Hg and >200 mm Hg or Respiratory Rate (RR) ≥30 breaths/min or SpO2 < 93 percent in air at rest. Note: Patients given continous positive airway pressure (CPAP) ventilator support are eligible for inclusion Presence of hyperinflammation defined as: 1. Lymphocyte counts: < 1000 cells/µL, in patients who have not received systemic glucocorticoids for at least 2 days prior to the assessment of the lymphocyte count < 1200 cells/µL, in patients who have received systemic glucocorticoids for at least 2 days prior to the assessment of the lymphocyte count and 2. One of the following three criteria: i. Ferritin > 500ng/mL ii. LDH > 300 U/L iii. D-Dimers > 1000 ng/mL
Exclusion criteria	Patients in mechanical ventilation or with modified early warning score (MEWS) >4 with evidence of moderate or above ARDS (Berlin definition, namely with PaO2/FiO2 >100, but <200 mm Hg) or severe respiratory insufficiency or evidence of rapid worsening (respiratory distress requiring mechanical ventilation or presence of shock or presence of concomitant organ failure requiring ICU admission). Note: For the evaluation of patient eligibility, temperature will not be considered in the calculation of the total MEWS score since presence of fever is a hallmark of SARS-CoV-2 infection Impairment of cardiac function defined as poorly controlled heart diseases, such as New York heart association (NYHA) class II (mild) and above, cardiac insufficiency, unstable angina pectoris, myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia need treatment or intervention Severe renal dysfunction (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m2) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis Uncontrolled hypertension (seated systolic blood pressure >180 mmHg, or diastolic blood pressure >110mmHg) Administration of plasma from convalescent patients who recovered from SARS-CoV-2 infection Clinical suspicion of latent tuberculosis History of hypersensitivity or allergy to any component of the study drug Pregnant women Existence of any life-threatening co-morbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion Enrollment in another concurrent clinical interventional study, or intake of an investigational drug within three months or 5 half-lives prior to inclusion in this study, if considered interfering with this study objectives as assessed by the Investigator Foreseeable inability to cooperate with given instructions or study procedures Clinical suspicion of active mycobacteria, histoplasma capsulatum, herpes zoster, salmonella, and shigella Infections Patients with liver dysfunction defined as AST or ALT > 5 × ULN
Interventions
	Treatment Emapalumab Initial dose: 6 mg/kg IV infusion on day 1. Maintenance dose: 3 mg/kg IV infusion every 3rd day on days 4, 7, 10, 13. Anakinra 100 mg IV infusion 4 times daily for 15 days
	Control Standard care
Participants
	Randomized participants : Emapalumab=5 Anakinra=5 Standard care=6
	Characteristics of participants N= 16 Mean age : NR 14 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=16 Critical: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register Number of Participants With Treatment Success [ Time Frame: Up to Day 15 ] Defined as the number of patients not requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)
	In the report NR
Documents available	Protocol Yes. In English Statistical plan Yes 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	Some concerns
General comment	This is an unpublished trial whose results have been reported in ClinicalTrials.gov. The trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. The trial was registered prospectively and no important changes were made to primary or secondary outcomes after recruitment start. The trial (n = 16) did not achieve its target sample size (n = 52) and is underpowered to assess statistical significance between the treatment and placebo group. The trial was terminated Quote: "Standard of care evolved during the timeframe of the study and had critical impact on recruitment. Early termination was not based on safety reasons but due to the reasons mentioned above. The ongoing patients were completed."