COURAGE-2 Study

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Efficacy and safety of co-administration of EGF + GHRP-6 in the treatment of acute cerebral infarction of ischemic etiology.

Secondary indentifying numbers:

IG/CIGB-845I/IC/1902

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB)

Source(s) of monetary or material support:

Center for Genetic Engineering and Biotechnology (CIGB), Havana. Ministry of Public Health, Cuba.

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Reference number:

In process

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Juan

Midle name:

Humberto

Last name:

Gutierrez Ronquillo

Medical Specialty :

2nd grade specialist in Neurology

Affiliation:

University Hospital "Arnaldo Milian"

Postal address:

Calle Nuevo Hospital, entre Doble Via y Circunvalacion

City:

Santa Clara

País:

Cuba

Zip Code:

50100

Telephone:

+53-42273420

Email address:

juanhgr@infomed.sld.cu [1]

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Havana, Medical Surgical Research Center, Giselle Leal Alpizar, 1st Degree Specialist in Internal Medicine.

Mayabeque, General Hospital "Leopoldito Martinez", Alberto Brito Cruz, 2nd Degree Specialist in Intensive Medicine and Emergencies.

Matanzas, University Hospital "Faustino Perez", Amaury del Puerto Cruz, 1st degree Specialist in Intensive and Emergency Medicine.

Cienfuegos, University Hospital "Dr. Gustavo Aldereguia ", Juan Ibrahim Garcia Leonard, 1st Degree Specialist in Neurology.

Villa Clara, General Hospital "Martires of April 9", Jorge Luis Alonso Freire, 1st Degree Specialist in Internal Medicine.

Sancti Spiritus, General Hospital "Camilo Cienfuegos", Ilietys Borroto Carpio, 1st Degree Specialist in Neurology.

Ciego de Avila, General Hospital "Dr. Antonio Luaces ", Donner Estenoz Garcia, 1st Degree Specialist in Neurology.

Ciego de Avila, General Hospital "Roberto Rodriguez", Luis Antonio Rodriguez Sanchez, PhD of Medical Sciences, 2nd Degree Specialist in Internal Medicine.

Camaguey, University Hospital "Manuel Ascunce", Nayade Perez Rodriguez, 1st Degree Specialist in Neurology.

Holguín, "Lucia Inniguez" Surgical Clinical Hospital, Ana Margarita Manzo Lopez, 1st Degree Specialist in Internal Medicine.

Granma, University Hospital "Carlos Manuel de Cespedes", Alexis Suarez Quesada, 2nd Degree Specialist in Internal Medicine and in Intensive Care and Emergencies.

Granma, Clinical Surgical Hospital "Celia Sanchez", Yoandra Fuentes Gonzalez, 1st Degree Specialist in Internal Medicine.

Santiago de Cuba, General Hospital "Juan Bruno Zayas", Elizabeth Lobaina Suarez, 1st Degree Specialist in Internal Medicine.

Santiago de Cuba, Provincial Hospital "Saturnino Lora", Elizabet Colina Avila, Specialist of 1st degree in Neurology.

Guantánamo, General Hospital "Agostinho Neto", Rogelio Creagh Bandera, PhD of Pedagogical Sciences, 2nd Degree Specialist in Internal Medicine.

Research ethics committees:

University Hospital "Arnaldo Milian", January 24, 2019.

Medical Surgical Research Center, February 21, 2019.

General Hospital "Leopoldito Martinez", January 10, 2019.

University Hospital "Faustino Perez", February 6, 2019.

University Hospital "Dr. Gustavo Aldereguia ", February 1, 2019.

General Hospital "Martires of April 9", January 10, 2019.

General Hospital "Camilo Cienfuegos", January 17, 2019.

General Hospital "Dr. Antonio Luaces ", January 17, 2019.

General Hospital "Roberto Rodriguez", February 13, 2019.

University Hospital "Manuel Ascunce", January 25, 2019.

"Lucia Inniguez" Surgical Clinical Hospital, January 23, 2019.

University Hospital "Carlos Manuel de Cespedes", January 16, 2019.

Clinical Surgical Hospital "Celia Sanchez", January 25, 2019.

General Hospital "Juan Bruno Zayas", January 24, 2019.

Provincial Hospital "Saturnino Lora", January 21, 2019.

General Hospital "Agostinho Neto", January 18, 2019.

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Pending

Date of first enrollment:

03/06/2019

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Acute cerebral infarction of ischemic etiology

Health condition(s) code:

Cerebral Infarction

Brain Infarction

Brain Ischemia

Stroke

Cerebrovascular Disorders

Vascular Diseases

Cardiovascular Diseases

Brain Diseases

Central Nervous System Disease

Nervous System Diseases

Intervention(s):

Group I (experimental): Serendictus (75 μg of recombinant epidermal growth factor [EGF] combined with 5.0 mg of the growth hormone releasing peptide [GHRP-6]) + conventional treatment. Serendictus will be administered intravenously, in bolus, slowly for 3 minutes a 1st dose at the time of inclusion in the study and then every 12 hours for 7 days (14 administrations in total). Group II (control group): Conventional treatment (among other general measures, includes: stabilization of the patient [breathing and circulation], correction of the water balance and electrolyte alterations, strict control of vital signs, placement of the patient in the supine position with the raised head at 30º [cerebral edema treatment], specific antibiotic therapy, maintain glycemic figures below 150 mmol/L and maintain adequate oxygenation of the patient).

Intervention code:

Epidermal Growth Factor

Growth Hormone-Releasing Hormone

Peptides

Administration, Intravenous

Intervention keyword:

Serendictus, Recombinant Epidermal Growth Factor, GHRP-6

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

Neurological status-disability (It will be evaluated according to the Rankin scale in 0: No symptoms; 1: No significant involvement despite the symptoms, possibility of performing all the activities of daily life; 2: Light disability, can not perform all the activities of daily life, but is able to attend to their bodily needs without help; 3: Moderate disability, requiring some help to satisfy their bodily needs but able to walk without help: 4: Moderately severe disability, inability to wander without help and to attend to their needs. bodily needs without help, 5: severe disability, bedridden, incontinent and with constant need for nursing care and attention). Measurement time: at discharge, and in months 1, 3, 6 and 12.

Key secondary outcomes:

Survival (alive, dead). Measurement time: at hospital discharge and during follow-up in months 1, 3, 6 and 12. Level of neurological deficit (It will be measured through the scale of NIHSS (National Institute of Heath Stroke Scale): Measurement time: to inclusion and hospital discharge. Ability to perform daily activities (It will be assessed through the Barthel index that measures the degree of dependence on the basic activities of daily life and a value ≥ 85 will be considered favorable, independence with minimal help). Measurement time: at 3, 6 and 12 months. Infarct volume (by Computerized Axial Tomography). Measurement time: to the inclusion, to the 4th, to the 8th and to the 30 days of the beginning of the treatment. Adverse clinical events (AE). They will be measured as: -AE occurrence (Yes, No), -AE description (event name), -AE intensity (mild, moderate, severe), -Relation of causality (unrelated, doubtful, possible, probable, definitive), -Measures taken (None, Administration of any pharmacological therapy, Addition of a non-pharmacological therapy, Exit of the study, Hospitalization / prolongation of the hospitalization), -Result (Completely resolved, Resolved with sequelae, Conditions in improvement, Condition present and unchanged, Worsening, Death caused by this event). Measurement time: daily in Week 1 and in months 1, 3, 6 and 12. Laboratory (numerical values of hemochemical tests: blood count, hematocrit, differential leukogram, platelet count, coagulogram, ALAT, ASAT, glycemia, creatinine, urea, uric acid, alkaline phosphatase, total proteins, albumin, bilirubin and cholesterol). Measurement time: at the beginning, on the 8th day (at discharge) and on the evaluations corresponding to months 1 and 6. Efficiency of Serendictus in the treatment of acute cerebral infarction of ischemic etiology, through the evaluation of incremental cost effectiveness (defined as the difference between the costs of the treatments that are compared on the difference between the effects of the therapy). Measurement time: at the end of the study.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

19 years

Maximum age:

80 years

Inclusion criteria:

1. Compliance with the diagnostic criteria (patients of both sexes, with a focal neurological defect caused by disturbances of the circulatory supply to a specific brain area, confirmed by computerized axial tomography images). 2. Age between 19 and 80 years, both inclusive. 3. Time between the onset of symptoms and the beginning of the administration of Serendictus less than 12 hours. 4. Voluntariness of the patient (or family member) through the granting of informed consent (oral).

Exclusion criteria:

1. Coma state (Glasgow scale less than 8). 2. Score on the NIHSS scale <5 or > 20. 3. When the neurological defect can be explained by another entity different from the acute cerebral infarction. 4. Patients with neurological symptoms or signs that return to normal before the start of treatment. 5. Severe and uncontrolled arterial hypertension (systolic >200 mmHg or diastolic> 120 mmHg) that does not descend after treatment. 6. Arterial hypotension (systolic <95 mmHg) that does not respond to the usual treatment. 7. How to install the clinical picture with seizures. 8. Patients with basic neurological alterations that could interfere with the functional evaluation process during the course of the study. 9. Patients diagnosed with malignant neoplasms. 10. Pregnancy or lactation at the time of inclusion in the study (referred by the patient or family member). 11. Obvious mental inability to issue consent and act accordingly with the study.

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

Randomized controlled trial

Masking:

Open

Control group:

Active

Study design:

Parallel

Phase:

Target sample size:

220

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Francisco

Last Name:

Hernandez Bernal

Specialty:

Doctor of Medical Sciences. 2nd Degree Specialist in Hygiene and Epidemiology.

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

Ave. 31 entre 158 y 190, Cubanacan, Playa.

City:

Havana

País:

Cuba

Zip Code:

11300

Telephone:

+53-72085887, 72087465

Email :

hernandez.bernal@cigb.edu.cu [2]

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Francisco

Last Name:

Hernandez Bernal

Specialty:

Doctor of Medical Sciences. 2nd Degree Specialist in Hygiene and Epidemiology.

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

Ave. 31 entre 158 y 190, Cubanacan, Playa.

City:

Havana

País:

Cuba

Zip Code:

11300

Telephone:

+53-72085887, 72087465

Email :

hernandez.bernal@cigb.edu.cu [2]

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000300

Date of Registration in Primary Registry:

14/03/2019

Record Verification Date:

2020/10/21

Next update date:

2021/10/21

Link to the spanish version:

Click here [3]