Clinical trial NCT06585319: Pirfenidone LP or Collagen-polyvinylpyrrolidone in COVID-19
Official title: Pilot Study of Kitoscell LP (pirfenidone LP) Vs Collagen-polyvinylpyrrolidone As Treatment and Protection in Patients with Moderate to Severe COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID 19
Keywords: collagen-polyvinylpyrrolidone
pirfenidone
survival
immunomodulation
Lead sponsor: Materno-Perinatal Hospital of the State of Mexico
Sponsor class: OTHER
First posted: 2024-09-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients were assigned one of the following treatments: pirfenidone (KitosCell tabs, CellPharma S de RL de CV. Mexico City, Mexico) 1,200 mg of oral q12 h or collagen-PVP (Fibroquel, Aspid SA de CV, Mexico City, Mexico) 2 ml intramuscular q24 h, for 7 days; control group was of patients without pirfenidone or collagen-PVP. Body temperature, heart rate, respiratory rate, pSO2%, PCO2, and pO2, hematic biometry, serum concentrations of glucose, uric acid, cholesterol, and triacyl glycerides, IFN-γ, TNF-α, IL-2, -4, -10, -13 and -17 were measured at the beginning and after 7 days of treatment.
Primary purpose: TREATMENT

Brief summary: Collagen-polyvinylpyrrolidone (collagen-PVP) and pirfenidone have the ability to control cytokine storms. This work explores the therapeutic effects of both, on the early treatment of patients with severe COVID-19. The hospital stay, quick COVID-19 severity index (qCSI) and admission to the ICU were statistically significantly lower when the patients were treated with collagen-PVP or pirfenidone, compared to the controls treated with dexamethasone alone.

Detailed description: The therapeutic target of COVID-19 is focused on the control of inflammation and the prevention of fibrosis. Collagen-polyvinylpyrrolidone (collagen-PVP) and pirfenidone have the ability to control cytokine storms observed in rheumatic and fibrotic disorders. In this work, the investigators explored the therapeutic effects of both, in addition to dexamethasone, on the early treatment of patients with severe COVID-19. The hospital stay, quick COVID-19 severity index (qCSI) and admission to the ICU were statistically significantly lower when the patients were treated with collagen-PVP or pirfenidone, compared to the controls treated with dexamethasone alone. Furthermore, only collagen-PVP normalized serum glucose at discharge. Since the intracellular mechanism of action of pirfenidone is partially known, it was performed a whole human genome microarray assay with total RNA isolated from fibroblast and macrophage cultures treated with collagen-PVP. Ingenuity Pathway Analysis showed that cell cycle, inflammation, and cell surface-extracellular matrix interaction could be regulated by the collagen-PVP copolymer, by down-regulation of pro-inflammatory cytokines, such as IL-6 and -8, while Th2 anti-inflammatory response signaling could be up-regulated. Additionally, down-regulation of some of the genes involved in nitric oxide production by inducible nitric oxide synthase showed a possible control for JAK, in the IFN-γ pathway, allowing the possibility of controlling inflammation through the JAK/STAT pathway, as has been observed for pirfenidone and other immunomodulators, such as ruxolitinib. In summary, once again, collagen-PVP and pirfenidone have demonstrated to favor inflammatory control and stand out as a possible therapy for inflammatory disorders derived from viral or microorganism infections.

Eligibility criteria: Inclusion Criteria:

* patients infected with SARS-CoV-2, hospitalized, with total bilirubin ≤1.5

Exclusion Criteria:

* if the patient underwent treatment with biological antirheumatic drugs, disease modifiers (DMARDs) or other immunosuppressive agents, patients who required continuous therapy with systemic corticosteroids in a dose greater than 10 mg of prednisone per day or equivalent; pregnant women, calculated creatinine clearance (or estimated glomerular filtration rate less than 10 ml/min or patients requiring renal replacement therapy

Primary outcomes:
measure: Number of patients that survived the COVID-19 infection
timeFrame: From enrollment until one month of follow up
Secondary outcomes:
Other outcomes:
Locations:
city: Toluca
country: Mexico
facility: Monica Pretelini Saenz Maternal Perinatal Hospital
state: State of Mexico
Study officials:
affiliation: Mónica Pretelini Sáenz Maternal Perinatal Hospital
name: Hugo Mendieta Zerón, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leyva-Gomez G, Lima E, Krotzsch G, Pacheco-Marin R, Rodriguez-Fuentes N, Quintanar-Guerrero D, Krotzsch E. Physicochemical and functional characterization of the collagen-polyvinylpyrrolidone copolymer. J Phys Chem B. 2014 Aug 7;118(31):9272-83. doi: 10.1021/jp502476x. Epub 2014 Jul 30.
citation: Olmos-Zuniga JR, Silva-Martinez M, Jasso-Victoria R, Baltazares-Lipp M, Hernandez-Jimenez C, Buendia-Roldan I, Jasso-Arenas J, Martinez-Salas A, Calyeca-Gomez J, Guzman-Cedillo AE, Gaxiola-Gaxiola M, Romero-Romero L. Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-beta1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing. Biomed Res Int. 2017;2017:6471071. doi: 10.1155/2017/6471071. Epub 2017 May 11.
citation: Furuzawa-Carballeda J, Cabral AR, Zapata-Zuniga M, Alcocer-Varela J. Subcutaneous administration of polymerized-type I collagen for the treatment of patients with rheumatoid arthritis. An open-label pilot trial. J Rheumatol. 2003 Feb;30(2):256-9.
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