PMID- 35757326
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 9
DP  - 2022
TI  - Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas 
      Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical 
      Trial.
PG  - 864837
LID - 10.3389/fcvm.2022.864837 [doi]
LID - 864837
AB  - 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].
CI  - Copyright (c) 2022 Macedo, Larocca, Noya-Rabelo, Aras, Macedo, Moreira, Caldas, 
      Torreao, Monsao, Souza, Vasconcelos, Bezerra, Petri, Souza, Pacheco, Daher, 
      Ribeiro-dos-Santos and Soares.
FAU - Macedo, Carolina T
AU  - Macedo CT
AD  - Department of Cardiology, Hospital Sao Rafael, Salvador, Brazil.
AD  - Goncalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.
AD  - Senai Institute on Innovation in Advanced Health Systems, SENAI CIMATEC, 
      Salvador, Brazil.
FAU - Larocca, Ticiana F
AU  - Larocca TF
AD  - Goncalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.
FAU - Noya-Rabelo, Marcia
AU  - Noya-Rabelo M
AD  - Department of Cardiology, Hospital Sao Rafael, Salvador, Brazil.
AD  - Escola Bahiana de Medicina e Saude Publica, Salvador, Brazil.
FAU - Aras, Roque Jr
AU  - Aras R Jr
AD  - University Hospital Professor Edgard Santos, Federal University of Bahia, 
      Salvador, Brazil.
FAU - Macedo, Cristiano R B
AU  - Macedo CRB
AD  - University Hospital Professor Edgard Santos, Federal University of Bahia, 
      Salvador, Brazil.
FAU - Moreira, Moises I
AU  - Moreira MI
AD  - Department of Cardiology, Hospital Sao Rafael, Salvador, Brazil.
FAU - Caldas, Alessandra C
AU  - Caldas AC
AD  - Department of Cardiology, Hospital Sao Rafael, Salvador, Brazil.
FAU - Torreao, Jorge A
AU  - Torreao JA
AD  - Department of Cardiology, Hospital Sao Rafael, Salvador, Brazil.
FAU - Monsao, Victor M A
AU  - Monsao VMA
AD  - Hospital Geral Roberto Santos, Salvador, Brazil.
FAU - Souza, Clarissa L M
AU  - Souza CLM
AD  - University Hospital Professor Edgard Santos, Federal University of Bahia, 
      Salvador, Brazil.
FAU - Vasconcelos, Juliana F
AU  - Vasconcelos JF
AD  - Goncalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.
AD  - Escola Bahiana de Medicina e Saude Publica, Salvador, Brazil.
FAU - Bezerra, Milena R
AU  - Bezerra MR
AD  - Senai Institute on Innovation in Advanced Health Systems, SENAI CIMATEC, 
      Salvador, Brazil.
FAU - Petri, Daniela P
AU  - Petri DP
AD  - Center for Biotechnology and Cell Therapy, Hospital Sao Rafael, Salvador, Brazil.
FAU - Souza, Bruno S F
AU  - Souza BSF
AD  - Goncalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.
AD  - Center for Biotechnology and Cell Therapy, Hospital Sao Rafael, Salvador, Brazil.
AD  - D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
FAU - Pacheco, Antonio G F
AU  - Pacheco AGF
AD  - Scientific Computing Program, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
FAU - Daher, Andre
AU  - Daher A
AD  - Vice-Presidency of Research and Reference Laboratories, Oswaldo Cruz Foundation, 
      Rio de Janeiro, Brazil.
FAU - Ribeiro-Dos-Santos, Ricardo
AU  - Ribeiro-Dos-Santos R
AD  - Goncalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.
AD  - Senai Institute on Innovation in Advanced Health Systems, SENAI CIMATEC, 
      Salvador, Brazil.
FAU - Soares, Milena B P
AU  - Soares MBP
AD  - Goncalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.
AD  - Senai Institute on Innovation in Advanced Health Systems, SENAI CIMATEC, 
      Salvador, Brazil.
LA  - eng
SI  - ClinicalTrials.gov/NCT02154269
PT  - Journal Article
DEP - 20220609
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC9222127
OTO - NOTNLM
OT  - Chagas cardiomyopathy
OT  - G-CSF therapy
OT  - NYHA functional class
OT  - cardiac functional analysis
OT  - safety study
COIS- 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.
EDAT- 2022/06/28 06:00
MHDA- 2022/06/28 06:01
PMCR- 2022/01/01
CRDT- 2022/06/27 04:22
PHST- 2022/01/28 00:00 [received]
PHST- 2022/04/26 00:00 [accepted]
PHST- 2022/06/27 04:22 [entrez]
PHST- 2022/06/28 06:00 [pubmed]
PHST- 2022/06/28 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2022.864837 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2022 Jun 9;9:864837. doi: 10.3389/fcvm.2022.864837. 
      eCollection 2022.