Pirfenidone LP or Collagen-polyvinylpyrrolidone in COVID-19

Materno-Perinatal Hospital of the State of Mexico

Status and phase: Completed; Phase 3; Phase 2

Conditions: COVID 19

Treatments: Drug: Pirfenidone 1200 mg; Drug: Collagen-polyvinylpyrrolidone

Study type: Interventional

Funder types: Other

Identifiers

NCT06585319

2020-12-713

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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36 participants in 3 patient groups

Collagen-polyvinylpyrrolidone

Experimental group

Description:

Collagen-PVP ml intramuscular q24 h

Treatment:

Drug: Collagen-polyvinylpyrrolidone

Pirfenidone

Active Comparator group

Description:

Pirfenidone 1,200 mg of oral q12 h

Treatment:

Drug: Pirfenidone 1200 mg

Control

No Intervention group

Description:

Standard treatment with dexamethasone (intravenously) and 40 or 60 mg of enoxaparin (subcutaneously, according to the patient's weight) once daily and 1 g of paracetamol