Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Autor:	Macedo CT; Department of Cardiology, Hospital São Rafael, Salvador, Brazil.; Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.; Senai Institute on Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador, Brazil., Larocca TF; Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil., Noya-Rabelo M; Department of Cardiology, Hospital São Rafael, Salvador, Brazil.; Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil., Aras R Jr; University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Brazil., Macedo CRB; University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Brazil., Moreira MI; Department of Cardiology, Hospital São Rafael, Salvador, Brazil., Caldas AC; Department of Cardiology, Hospital São Rafael, Salvador, Brazil., Torreão JA; Department of Cardiology, Hospital São Rafael, Salvador, Brazil., Monsão VMA; Hospital Geral Roberto Santos, Salvador, Brazil., Souza CLM; University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Brazil., Vasconcelos JF; Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.; Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil., Bezerra MR; Senai Institute on Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador, Brazil., Petri DP; Center for Biotechnology and Cell Therapy, Hospital São Rafael, Salvador, Brazil., Souza BSF; Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.; Center for Biotechnology and Cell Therapy, Hospital São Rafael, Salvador, Brazil.; D'Or Institute for Research and Education, Rio de Janeiro, Brazil., Pacheco AGF; Scientific Computing Program, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Daher A; Vice-Presidency of Research and Reference Laboratories, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Ribeiro-Dos-Santos R; Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.; Senai Institute on Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador, Brazil., Soares MBP; Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.; Senai Institute on Innovation in Advanced Health Systems, SENAI CIMATEC, Salvador, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2022 Jun 09; Vol. 9, pp. 864837. Date of Electronic Publication: 2022 Jun 09 (Print Publication: 2022).
DOI:	10.3389/fcvm.2022.864837
Abstrakt:	Aim: Previous studies showed that granulocyte-colony stimulating factor (G-CSF) improved heart function in a mice model of Chronic Chagas Cardiomyopathy (CCC). Herein, we report the interim results of the safety and efficacy of G-CSF therapy vs. placebo in adults with Chagas cardiomyopathy. Methods: Patients with CCC, New York Heart Association (NYHA) functional class II to IV and left ventricular ejection fraction (LVEF) 50% or below were included. A randomization list using blocks of 2 and 4 and an allocation rate of 1:1 was generated by R software which was stratified by functional class. Double blinding was done to both arms and assessors were masked to allocations. All patients received standard heart failure treatment for 2 months before 1:1 randomization to either the G-CSF (10 mcg/kg/day subcutaneously) or placebo group (1 mL of 0.9% saline subcutaneously). The primary endpoint was either maintenance or improvement of NYHA class from baseline to 6-12 months after treatment, and intention-to-treat analysis was used. Results: We screened 535 patients with CCC in Salvador, Brazil, of whom 37 were randomized. Overall, baseline characteristics were well-balanced between groups. Most patients had NYHA class II heart failure (86.4%); low mean LVEF was 32 ± 7% in the G-CSF group and 33 ± 10% in the placebo group. Frequency of primary endpoint was 78% (95% CI 0.60-0.97) vs. 66% (95% CI 0.40-0.86), p = 0.47, at 6 months and 68% (95% CI 0.43-0.87) vs. 72% (95% CI 0.46-0.90), p = 0.80, at 12 months in placebo and G-CSF groups, respectively. G-CSF treatment was safe, without any related serious adverse events. There was no difference in mortality between both arms, with five deaths (18.5%) in treatment vs. four (12.5%) in the placebo arm. Exploratory analysis demonstrated that the maximum rate of oxygen consumption during exercise (VO 2 max) showed an improving trend in the G-CSF group. Conclusion: G-CSF therapy was safe and well-tolerated in 12 months of follow-up. Although prevention of symptom progression could not be demonstrated in the present study, our results support further investigation of G-CSF therapy in Chagas cardiomyopathy patients. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02154269]. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Macedo, Larocca, Noya-Rabelo, Aras, Macedo, Moreira, Caldas, Torreão, Monsão, Souza, Vasconcelos, Bezerra, Petri, Souza, Pacheco, Daher, Ribeiro-dos-Santos and Soares.)
Databáze:	MEDLINE
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