Evaluation of G-CSF (Colony Stimulating Factor) in Patients With Chronic Chagas Cardiomyopathy

Prospective, Double-blind, Randomized, Placebo-controlled Phase II Clinical Trial for Evaluation of G-CSF in Patients With Chronic Chagas Cardiomyopathy

The purpose of this study is to evaluate the effectiveness of treatment with G-CSF in patients with chronic heart failure secondary to Chagas disease.

Study Overview

• Status: Completed
• Conditions: Chronic Chagasic Myocarditis
• Intervention / Treatment: Drug: Treatment with G-CSF (Granulocyte colony stimulating factor); Drug: Placebo saline

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
      • Hospital Sao Rafael

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Chagas' disease confirmed by two serological tests with different methodologies;
• Diagnosis of Chagas' cardiomyopathy in NYHA functional classes II, III and IV of heart failure;
• Availability and willingness to participate, given the schedule of the study;
• Agreement and signing the written form.

Exclusion Criteria:

• Acute systemic infections
• Solid neoplasms, myelodysplastic syndrome, acute or chronic myeloid leukemia, confirmed by imaging studies or past medical history;
• Valvulopathies with hemodynamic consequences;
• Autoimmune, pulmonary, or degenerative diseases, confirmed by imaging studies or past medical history;
• Severe renal, hepatic or thyroid dysfunction, confirmed by imaging studies or past medical history;
• Pregnancy (confirmed by examination of β HCG) or lactation;
• Known hypersensitivity to G-CSF or to other components of the formula and / or hypersensitivity to proteins derived from E. coli.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: G-CSF; Subjects will be randomly assigned to receive treatment with G-CSF (10mg/kg/day) for five days, during 4 cicles.	Drug: Treatment with G-CSF (Granulocyte colony stimulating factor); Subjects will be randomly assigned to receive treatment with G-CSF (10mg/kg/day) for five days, during 4 cicles.; Other Names: G-CSF
Placebo Comparator: Saline; Subjects will be randomly assigned to receive saline for five days, during 4 cicles.	Drug: Placebo saline; Subjects will be randomly assigned to receive treatment saline for five days, during 4 cicles.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NYHA (New York Heart Association) functional class improvement	All patients will undergo periodic clinical evaluations in order to identify improvement on NYHA classification for heart failure.	6, 9 and 12 months after the therapy with G-CSF

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of cardiovascular function measured by transthoracic echocardiography	All patients will be submitted to echocardiography after 6 and 12 months to assess improvements on ventricular function.	6 and 12 months after the therapy
Assessment of cardiovascular function measured by cardiac magnetic resonance imaging	All patients will be submitted to a second cardiac magnetic resonance, after 12 months, to assess improvements on left ventricular ejection fraction.	12 months after therapy
Evaluation of functional capacity assessed by treadmill test and by 6-minute walk test	All patients will be submitted to a second treadmill test and 6-minute walk test after 12 months to assess improvement on functional capacity.	12 months after the therapy
Evaluation of improvement of quality of life	All patients will respond to Minnesota Questionnaire to have an evaluation of quality of life after 6 and 12 months.	6 and 12 months after the therapy
Determination of tolerability	All patients will be submitted to complete blood counts in several time frames in order to evaluate tolerability to G-CSF injection.	1, 5, 13, 17, 25, 29, 37 and 41 days and 3, 6, 9 and 12 months after the therapy

Collaborators and Investigators

• Sponsor: Hospital Sao Rafael
• Investigators: Study Director: Ticiana F Larocca, MD, Msc, Hospital Sao Rafael; Study Chair: Ricardo Ribeiro-dos-Santos, PhD, Hospital Sao Rafael; Study Chair: Luís Cláudio L Correia, MD, Msc, Hospital Sao Rafael; Study Chair: Carolina T Macedo, MD, MSc, Hospital Sao Rafael; Study Chair: Clarissa LM Souza, MD, Hospital Sao Rafael

Publications and helpful links

General Publications

• Macedo CT, Larocca TF, Noya-Rabelo M, Aras R Jr, Macedo CRB, Moreira MI, Caldas AC, Torreao JA, Monsao VMA, Souza CLM, Vasconcelos JF, Bezerra MR, Petri DP, Souza BSF, Pacheco AGF, Daher A, Ribeiro-Dos-Santos R, Soares MBP. Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial. Front Cardiovasc Med. 2022 Jun 9;9:864837. doi: 10.3389/fcvm.2022.864837. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: May 30, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimate): June 3, 2014

Study Record Updates

• Last Update Posted (Actual): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 21, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Cell therapy; G-CSF; Chagas disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Chagas Disease; Trypanosomiasis; Euglenozoa Infections; Myocarditis; Cardiomyopathies; Chagas Cardiomyopathy; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: PCL07/12