RESUMO
BACKGROUNDCurrently, therapeutic options for ambulatory COVID-19 patients are limited. OBJECTIVETo evaluate the safety, efficacy and effect of the intramuscular administration of polymerized type I collagen (PTIC) on hyperinflammation, oxygen saturation and symptom improvement in adult outpatients with symptomatic COVID-19. DESIGNDouble-blind, randomised, placebo-controlled clinical trial of PTIC vs placebo. SETTINGSingle Third-level hospital in Mexico City (Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran) PARTICIPANTSEighty-nine adult participants with a confirmed COVID-19 diagnosis and symptom onset within the 7 days preceding recruitment were included from August 31, 2020 to November 7, 2020 and followed for 12 weeks. Final date of follow-up was February 4, 2021. INTERVENTIONSPatients were randomly assigned to receive either 1.5 ml of PTIC intramuscularly every 12 h for 3 days and then every 24 h for 4 days (n=45), or matching placebo (n=44). MAIN OUTCOMES AND MEASURESThe primary outcome was a mean reduction of at least 50% in the level of IP-10 compared to baseline. The secondary outcomes were mean oxygen saturation [≥]92% while breathing ambient air and duration of symptoms. RESULTSOf 89 patients who were randomised, 87 (97.8%) were included in an intention-to-treat analysis; 37 (41.6%) were male and mean age was 48.5{+/-}14.0 years. The IP-10 levels decreased 75% in the PTIC group and 40% in the placebo group vs baseline. The comparison between treatment vs placebo was also statistically significant (P=0.0047). The IL-8 (44%, P=0.045), M-CSF (25%, P=0.041) and IL-1Ra (36%, P=0.05) levels were also decreased in the PTIC group vs baseline. Mean oxygen saturation [≥]92% was achieved by 40/44 (90%), 41/42 (98%) and 40/40 (100%) of participants that received PTIC at 8, 15 and 97 days of follow-up vs 29/43 (67%), 31/39 (80%) and 33/37 (89%) of patients treated with placebo (P=0.001). The unadjusted accelerated failure time model showed that patients treated with PTIC achieved the primary outcome 2.70-fold faster (P<0.0001) than placebo. In terms of risk, the group of patients treated with PTIC had a 63% lower risk of having a mean oxygen saturation <92% vs placebo (P<0.0001). Symptom duration in patients treated with PTIC was reduced by 6.1{+/-}3.2 days vs placebo. No differences in adverse effects were observed between the groups at 8, 15 and 97 days of follow-up. CONCLUSIONSIn this study, treatment with PTIC down-regulated IP-10, IL-8, M-CSF and IL-Ra levels, which could explain the PTIC effect on the higher proportion of patients with mean oxygen saturation readings [≥]92% and a shorter duration of symptoms as compared to patients treated with placebo. Although results are encouraging, larger randomised trials are needed. TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT04517162
