Hydroxychloroquine in Combination With Sirolimus and Dexamethasone for Treating COVID-19 Patients
Status:
Not yet recruiting
Trial end date:
2022-09-01
Target enrollment:
Participant gender:
Summary
COVID-19 caused an unprecedented international crisis. There is an urgent need for an
effective regimen to cure this illness. Anecdotal data and some prospective results suggested
a role of antimalarial drugs (chloroquine and hydroxychloroquine) in the treatment of this
disease with best available data showing value of adding azithromycin. Based on drug
repurposing studies done by our team and others, we identified the autophagy/apoptosis
pathway as a major target for intervention. Based on in-silico and in-vitro models, sirolimus
was identified as the drug that deserves urgent prioritization. The rational for combining
sirolimus and hydroxychloroquine is explained in details in the study background below and a
short video prepared by study PI (https://youtu.be/-zlOMXJp2hg). The evidence for using
sirolimus for influenza is emphasized by a RCT that showed reduction of mechanical
ventilation time by 50% (7 days on sirolimus arm vs 15 days on oseltamivir/steroids arm).
Safe administration in human subjects is illustrated by multiple phase I/II clinical trials,
performed in patients with cancer. COVID19-HOPE trial will randomize patients to 2 arms:
HCQ/AZ (Arm A) and HCQ/SIR (Arm B). The main inclusion criteria is an RT-PCR test confirming
infection with SARS-CoV-2 along with objective clinical criteria of disease (fever, tachypnea
and/or hypoxemia). The primary endpoint of study will be Time To Clinical Improvement (TTCI),
defined as time from randomization to resolution of the clinical features mentioned above (no
fever, no tachypnea and no hypoxemia). In addition, secondary endpoints will include clinical
failure by day 28 (need for intubation and/or death), QT interval prolongation, and adverse
events. The estimated NNT based on Wilcoxon Mann Whitney comparison of TTCI in study arms is
58 patients (29 each arm). The study includes an adaptive plan, meaning that after different
time points the study results will be evaluated and the NNT and randomization scheme (1:1 vs.
others) will be evaluated and submitted to the IRB. Also, if one arm proves to be of no
value, another regimen might be introduced based on available data. The study will recruit
patients for a year and once approved by IRB and JFDA attempts to recruit other centers will
be made (including national and regional centers).