1115. Effect of polymerized type I collagen in hyperinflammation of adult outpatients with symptomatic COVID-19: a double blind, randomised, placebo-controlled clinical trial
Authors: Méndez-Flores Silvia , Priego-Ranero Angel , Azamar-Llamas Daniel , Olvera-Prado Héctor , Rivas-Redondo Kenia Ilián , Ochoa-Hein Eric , Pérez-Ortíz Andric , Rojas-Castañeda Estefano , Urbina-Terán Said , Septién-Stute Luis , Hernández-Gilsoul Thierry , Aguilar-Morgan Adrián Andrés , Fernández-Camargo Dheni Aidé , Olivares-Martínez Elizabeth , Hernández-Ramírez Diego Francisco , Torres-Villalobos Gonzalo , Furuzawa-Carballeda Janette , Rendón-Macías Mario Enrique , Del Carpio-Orantes Luis 
Published: December 2022

Abstract

Background
Currently, therapeutic options for outpatients with COVID-19 are limited, in Mexico Polymerized Collagen type I (PCTI) has been tested as a useful option.

Methods
Double-blind, randomised, placebo-controlled clinical trial of PTIC vs placebo. To 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. Eighty-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. Patients 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).

Results
Of 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&lt; 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 &lt; 92% vs placebo (P&lt; 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.

Conclusion
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 SaO2 ≥92% and a shorter duration of symptoms as compared with placebo.
Serum cytokine and chemokine levels of SARS-CoV2-infected symptomatic outpatients at baseline and day 8 post-treatment with PTIC or placebo. Data are expressed as median with 95% confidence. (A) IP-10, IFN-γ inducible protein-10; (B) IL-8, Interleukin-8; (C) M-CSF, Macrophage colony-stimulating factor; (D) IL-1Ra, IL-1 receptor antagonist; (E) TRAIL, TNF-related apoptosis inducing ligand; and (F) Forest plot (95% confidence intervals).
(A) Probability of oxygen saturation 92% or greater while breathing ambient air. (B) Accelerated time failure model for oxygen saturation 92% or greater while breathing ambient air among polymerised type I collagen and placebo.

Disclosures
All Authors: No reported disclosures.