Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences.
Different results were reported at IDWeek from the AIM results.
The study enrolled people with their last exposure within 4 days, i.e., if someone was exposed for 30 days in a row, they could be enrolled anywhere from day 1 to day 34. Therefore many were likely infected earlier than the enrollment date. Note that PCR has a very high false negative rates, e.g., 100% on day 1 and 67% on day 4 here .
50% of infections were detected by day 4. With the PCR false negatives and treatment delays it is likely that a majority of infections happened before enrollment or before HCQ can reach therapeutic levels.
Significantly more cases were caught at baseline in the control group (54 vs. 29 for HCQ) and excluded from analysis.
The early presentation stated that therapy started one day after enrollment and study supplies were sent to the participant "either by courier or mail". The published paper changes this to "courier delivery within 48 hours".
Overall delays are unclear but may be:
time since first exposure - unlimited
time from last exposure to enrollment - 10% reported as >= 5 days
time to telehealth meeting - 1 day (3 days if Friday enrollment?)
time to receive medication - <48 hours (including weekends?)
Symptomatic in this study was based on CDC-defined symptoms which contain symptoms that may be due to HCQ side effects.
Some results have not been reported, including symptomatic @28 days. The study uses a low dosage over an extended period, therapeutic levels may only be reached nearer to day 14, if at all, so day 28 results should be more informative when available (although labeled a PEP trial, with the low dosage and continuous exposure for most participants it is more of a PrEP/PEP trial where benefit might be seen later as HCQ levels increase).
PCR+ @28 days mITT - aHR 1.16 [0.77-1.73]
PCR+ @14 days mITT - aHR 1.10 [0.73-1.66] IDWeek report was different: aHR 0.99 [0.64-1.52]
PCR+ @14 days ITT - aHR 0.81 [0.57-1.14]
PCR+ symptomatic @28 days - NOT REPORTED YET
duration of shedding - NOT REPORTED YET
Not in study protocol:
PCR+ cumulative symptomatic @14 days - aHR 1.23 [0.76-1.99].
Dose in first 24 hours - 0.8g (compare with Boulware et al. 2g)
Dose in first 5 days - 1.6g (compare with Boulware et al. 3.8g)
Other research suggests vitamin C may be beneficial for COVID-19, e.g. . No information on severity of cases is provided. Binary PCR does not distinguish replication-competence. There were 2 COVID-19 hospitalizations, one in each group. Side effects were similar for HCQ and placebo. 83% medication adherence at day 14.
COVID-19 PEP. NCT04328961
Barnabas et al., 12/7/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 30 authors.
risk of hospitalization, 3.7% higher, RR 1.04, p = 1.00, treatment 1 of 407 (0.2%), control 1 of 422 (0.2%).
risk of COVID-19 case, 27.0% higher, RR 1.27, p = 0.33, treatment 43 of 353 (12.2%), control 33 of 336 (9.8%), adjusted per study, day 14 symptomatic mITT PCR+ AIM.
risk of COVID-19 case, 23.0% higher, RR 1.23, p = 0.41, treatment 40 of 317 (12.6%), control 32 of 309 (10.4%), adjusted per study, day 14 symptomatic mITT PCR+ IDWeek.
risk of COVID-19 case, 10.0% higher, RR 1.10, p = 0.66, treatment 53 of 353 (15.0%), control 45 of 336 (13.4%), adjusted per study, day 14 PCR+ mITT AIM.
risk of COVID-19 case, 1.0% lower, RR 0.99, p = 0.97, treatment 46 of 317 (14.5%), control 43 of 309 (13.9%), adjusted per study, day 14 PCR+ mITT IDWeek.
risk of COVID-19 case, 19.0% lower, RR 0.81, p = 0.23, treatment 82 of 387 (21.2%), control 99 of 393 (25.2%), adjusted per study, day 14 PCR+ ITT AIM.
Effect extraction follows pre-specified rules
prioritizing more serious outcomes. For an individual study the most serious
outcome may have a smaller number of events and lower statistical signficance,
however this provides the strongest evidence for the most serious outcomes
when combining the results of many trials.