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Table 1 Secondary Outcomes in the MIRACLE trial

From: Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial

OutcomeDefinition
28-day mortalityDeath from any cause within 28 days of enrollment
Hospital mortalityDeath from any cause in the index hospitalization
ICU mortalityDeath from any cause in index ICU admission.
Sequential Organ Failure Assessment scoresSOFA score on study days 0, 3, 7, 14, 21 and 28
Supplemental oxygen-free daysNumber of days within the first 28 days after enrollment when patients do not receive of supplemental oxygen. Patients who die within 28 days will be assigned the value “0”
Renal replacement therapy-free daysNumber of days within the first 28 days after enrollment when patients do not receive of renal replacement therapy. Patients who die within 28 days will be assigned the value “0”
Vasopressor-free daysNumber of days within the first 28 days after enrollment when patients do not receive of vasopressors. Patients who die within 28 days will be assigned the value “0”
Invasive or non-invasive mechanical ventilation-free daysNumber of days within the first 28 days after enrollment when patients do not receive of mechanical ventilation. Patients who die within 28 days will be assigned the value “0”
Organ support-free daysNumber of days within the first 28 days after enrollment when patients do not receive of invasive mechanical ventilation, renal replacement therapy and vasopressor. Patients who die within 28 days will be assigned the value “0”
Extracorporeal circulation support-free daysNumber of days within the first 28 days in which patients are not receiving extracorporeal circulation support. Patients who die within 28 days will be assigned the value “0”
ICU-free daysNumber of days in which patients are not being cared for in the ICU during the first 28 days after enrollment. Patients who die within 28 days will be assigned the value “0”
Post-randomization hospital length of stayNumber of days between randomization and discharge from the hospital. Because of the competing risk effect of death on length of stay, length of stay will be also reported for survivors alone
Renal replacement therapy at day 90Number and percentage of patients on renal replacement therapy at day 90
Oxygen supply at day 90Number and percentage of patients on oxygen supply at day 90
Non-invasive mechanical ventilation at day 90Number and percentage of patients on non-invasive mechanical ventilation at day 90
Invasive mechanical ventilation at day 90Number and percentage of patients on Invasive mechanical ventilation at day 90
Secondary laboratory outcomes
 Viral replication kineticsupE and ORF1 cycle thresholds of blood and respiratory samples
 Time to clearance from the lower respiratory tractNumber of days from randomization to MERS-CoV RNA clearance of respiratory samples defined as two negative RT-PCR results not followed by a positive one. Patients who die before clearance will be censored at the time of death
Safety outcomes
 Serious adverse event reports (SAE)The number and percentage of reported serious adverse events any time during the study period. These SAEs include: acute pancreatitis, severe elevation of Alanine aminotransferase (ALT) to more than five-fold the upper normal limit, anaphylaxis, bleeding diathesis and others
 Adverse EventsThe number and percentage of adverse events graded using the Common Terminology Criteria for Adverse Events, at any time within 28 days after enrollment. The adverse drug reactions include: allergic reactions, gastrointestinal, general nervous system and others. See also Table S6
Functional outcomes
 Karnofsky scoreKarnofsky Performance Status Scale for functional impairment, which is a scale from 100 (indicating “Normal,” no complaints; no evidence of disease) to 0 (indicating death) at day 90