MisterBlues schreef op 27 oktober 2020 17:13:
Dit is de samenvatting van het 21 patiënten open label onderzoek. (De resultaten hoeven niet zo goed te zijn als deze.)
Importance: There is currently no effective drug for Critical COVID-19 with Respiratory Failure, particularly in highly comorbid patients and mortality is in excess of 30%. Vasoactive Intestinal Peptide (VIP) blocks replication of the SARS-CoV-2 virus, inhibits cytokine synthesis, prevents cytopathy, and upregulates surfactant production in human pulmonary cells.
Objective: To determine the safety and efficacy of intravenous aviptadil (synthetic Vasoactive Intestinal Peptide) for improving survival and recovery from respiratory failure in patients with Critical COVID-19 and severe comorbidity who are ineligible for phase 3 trials of aviptadil.
Design: Prospective, open-label, administratively-controlled trial, measuring objective endpoints only. Patients were treated in June/July 2020. and followed for 60 days or more post ICU admission.
Setting: Intensive care unit and step down units of a quaternary care hospital
Participants: 21 consecutively admitted patients with Critical COVID-19, treated with intravenous aviptadil (synthetic VIP), compared to all patients with comparable comorbidity (n=24) from the same ICU, treated by the same clinical team, in the same time-frame who received maximal standard of care (SOC).
Intervention: 3 successive 12-hour intravenous infusions of aviptadil at 50/100/150 pmol/kg/hr.
Main Outcome Measures: Survival, Recovery from Respiratory Failure, WHO 10 point ordinal scale. Results: Nineteen of 21 patients survived to day 28 in the aviptadil-treated group compared to 4 of 24 control patients (90% vs 17%; P<.0001). Kaplan-Meier analysis demonstrates a 9-fold advantage in probability of survival (Hazard Ratio 0.113; 95% CL 0.037, 0.343). A similar 9-fold advantage was seen in cumulative probability of Recovery from Respiratory Failure (Hazard ratio: 0.115; 95% CL: 0.0254, 0.5219). A mean 6.1 point difference in the 10 point WHO Ordinal Scale for COVID-19 was seen between aviptadil-treated patients, who exhibited a 2.6 point mean improvement from time of ICU admission vs. those treated with standard of care who exhibited a mean 3.5 point mean decrement (Wilcoxon rank sum: P<.001). Improved radiographic appearance was seen in both lungs of 17 patients and in one lung of 2 treated patients. Four of 5 aviptadil-treated patients initially on Extracorporeal Membrane Oxygenation (ECMO) have been decannulated, compared to 3 of 13 ECMO-treated controls (80% vs. 23%;P=.045). A 75% (95% CI±3%: P<.001) reduction in IL-6 was seen.
Comment: A dramatic multi-dimensional treatment effect was observed, consistent with FDA and ICH-10 guidance for acceptance of externally-controlled, open-label trials in high-lethality conditions.