COVID 19
Conditions
Keywords
collagen-polyvinylpyrrolidone, pirfenidone, survival, immunomodulation
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.
Interventions
2 ml intramuscular q24 h
1,200 mg of oral q12 h
Sponsors
Materno-Perinatal Hospital of the State of Mexico
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients that survived the COVID-19 infection | From enrollment until one month of follow up | After each of the treatments that were given for seven days, the evolution of the patients was recorded. |
Countries
Mexico
Outcome results
None listed