Trial NCT04345614
Publication Miller J, Crit Care, 2020 (published paper)
Dates: 2020-04-08 to 2020-05-13
Funding: Private (CalciMedica, Inc. )
Conflict of interest: Yes
Methods | |
RCT Blinding: Unblinded | |
Location :
Multicenter / USA Follow-up duration (days): 30 | |
Inclusion criteria | Adults with a diagnosis of COVID-19 determined by reverse transcription polymerase chain reaction and pneumonia documented by chest imaging. In addition, patients were required to have ? 1 symptom consistent with COVID-19, such as fever, cough, sore throat, malaise, headache, muscle pain, dyspnea, confusion, or respiratory distress, and ? 1 clinical sign suggesting respiratory compromise, such as respiratory rate ? 30 breaths per minute, heart rate ? 125 bpm, SpO2 < 93% on room air or requiring > 2 L oxygen by nasal cannula to maintain SpO2 ? 93%, or PaO2/FiO2 < 300, imputed from pulse oximetry or determined by arterial blood gas |
Exclusion criteria | From the registry
1. Expected survival or time to withdrawal of life-sustaining treatments expected to be <7 days. 2. Do Not Intubate order; 3. Home mechanical ventilation (noninvasive ventilation or via tracheotomy) except for continuous positive airway pressure or bi-level positive airway pressure (CPAP/BIPAP) used solely for sleep-disordered breathing; 4. PaO2/FiO2 ? 100 at Screening or noted in the 24 hours before Screening. The PaO2/FiO2 may be estimated from pulse oximetry (Appendix 1) or determined by arterial blood gas; 5. High flow supplemental oxygen using a high flow nasal cannula; 6. Noninvasive positive pressure ventilation; 7. Invasive mechanical ventilation via endotracheal intubation or tracheostomy; 8. Extracorporeal membrane oxygenation (ECMO); 9. Shock defined by the use of vasopressors; 10. Multiple organ dysfunction or failure; 11. Positive Influenza A or B testing if tested as local standard of care; 12. Pathogens detected by a respiratory panel if tested as local standard of care; 13. The patient has a history of: a. Organ or hematologic transplant; b. HIV; c.Active hepatitis B, or hepatitis C infection; 14. Current treatment with: a. Chemotherapy; b. Immunosuppressive medications or immunotherapy (Section 5.3 for list of prohibited immunosuppressive medications and immunotherapy) at the time of consent; c. Hemodialysis or Peritoneal Dialysis; 15. Have a history of venous thromboembolism (VTE) (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 12 weeks prior to screening or have a history of recurrent (> 1) VTE; 16. The patient is known to be pregnant or is nursing; 17. Currently participating in another study of an investigational drug or therapeutic medical device at the time of consent; 18. Allergy to eggs or any of the excipients in study drug. |
Interventions | |
Treatment
Auxora Initial dose: 2.0 mg/kg IV infusion, maximum 250 mg followed by 1.6 mg/kg IV infusion, maximum 200 mg the next 2 days |
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Control
Standard care Definition of Standard care: All patients received local standard of care, including antiviral agents, but investigational therapies and immunosuppressive medications were not permitted. At the discretion of the site investigators, patients treated with either Auxora or standard of care alone were able to receive convalescent plasma if they required invasive mechanical ventilation. | |
Participants | |
Randomized 26 participants (n1=17 / n2= 9) | |
Characteristics of participants N=26 Mean age : 59.7 12 males Severity : Mild: n=0 / Moderate: n=26/ Severe: n=0 Critical: n=0 | |
Primary outcome | |
In the register Number of days from the Start of the First Infusion of Study Drug (SFISD) to recovery [ Time Frame: From start of first infusion of study drug to day 30 ] | |
In the report recovery rate defined as the first day the patient satisfied criterion 6, 7, or 8 of the 8-point ordinal scale | |
Documents available |
Protocol NR Statistical plan NR Data-sharing stated 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 all available versions of the published article, the study registry and supplementary appendix were used in data extraction and risk of bias assessment. The study was terminated early by the US Food and Drug Administration. As a result, the target sample size specified in the registry was not achieved. Quote "The FDA provided guidance on May 12, 2020, to limit further enrolment in the open-label study and transition to a randomized, blinded, placebo-controlled study, and as such, both arms A and B ceased further enrolment". The study reported the results in two arms based on severity of the disease. Data on the arm with patients requiring high flow oxygenation (Arm B) was not used in this review as the sample size (n=4) was too small. In the trial registration, the control treatment was intended to be Placebo but was Standard care in the published report. There was no change from the trial registration in the intervention and control treatments in the primary outcome. Some secondary outcomes (number of days in the ICU and CM4620-IE serum concentration) were reported in the registry and not in the published article. |