Revisions for DALIA Study | Registro Público Cubano de Ensayos Clínicos

--- 11 August 2020 - 12:41pm by Gladys
+++ 24 March 2023 - 7:27am by Gladys
-Av. Cuauhtemoc # 330, C.P. 06720, Mexico city, Mexico
+Av. Cuauhtemoc  330, C.P. 06720, Mexico city, Mexico
-/08/11
+/10/05
-/08/11
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Revision of 24 March 2023 - 7:27am:

DALIA 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:

Evaluation of the effect and safety of the CIGB-258 peptide in the treatment of seriously or critically ill patients due to COVID-19. (COVID-19)

Secondary indentifying numbers:

IG/CIGB-258I/CV/2001

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB)

Source(s) of monetary or material support:

Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico. Center for Genetic Engineering and Biotechnology (CIGB), Havana.

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:

Others instances

Other regulatory instances:

Federal Commission for the Protection against Sanitary Risks (COFEPRIS), Mexico.

Authorization date :

09/07/2020

Reference number:

203300410A0132/2020

Principal investigator

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

First name:

Juan

Midle name:

Carlos

Last name:

Anda Garay

Medical Specialty :

Master in Health Sciences; Titular Professor of Internal Medicine.

Affiliation:

Specialty Hospital from the Siglo XXI National Medical Center, IMSS, Mexico.

Postal address:

Avenida Cuauhtemoc # 330

City:

Mexico City

Country:

Mexico

Zip Code:

06720

Telephone:

+52-5556276900

Email address:

eduardoferat@me.com

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:

Mexico

Clinical sites:

Not applicable

Recruitment status

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

Recruitment status:

Pending

Date of first enrollment:

11/08/2020

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:

COVID-19 respiratory distress

Health condition(s) code:

Coronavirus Infections

SARS Virus

Coronaviridae Infections

Betacoronavirus

Severe Acute Respiratory Syndrome

Respiratory Tract Diseases

Health condition keyword:

COVID-19

Intervention(s):

- Group I: CIGB-258 peptide (Jusvinza, CIGB, Havana, Cuba) + standard therapy according to the interim algorithms for the care of COVID-19 established by the IMSS. Patients WITH mechanical ventilation: 1 mg intravenously every 12 hours until extubation of the patient. After weaning, administer 1 mg intravenously every 24 hours for three days. If there is no clinical, gasometric and radiological improvement after 24-48 hours, the dose can be increased to 2 mg, with a frequency of 12 hours (at the discretion of the practitioner). Total dose / day: 4 mg. Patients WITHOUT mechanical ventilation: 1 mg intravenously every 12 hours until the patient reverses his condition (no need for oxygen therapy, or signs and / or symptoms of acute respiratory failure). If at 72 hours there is no clinical, gasometric and radiological improvement (or earlier, if the patient requires mechanical ventilation), the dose can be increased to 2 mg, with a frequency of 12 hours (at the discretion of the practitioner). Total dose / day: 4 mg. If after the 7th day of a patient receiving the maximum dose of CIGB-258 peptide (2 mg every 12 hours) no clinical, gasometric and radiological improvement is observed, the doctor may consider suspending this therapy or not (and start another treatment out of protocol). - Group II (Control): Standard therapy according to the interim algorithms for COVID-19 care established by the IMSS.

Intervention code:

Peptides

Respiration, Artificial

Administration, Intravenous

Intervention keyword:

Jusvinza, CIGB-258

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):

1) Mortality on discharge from the Hospital (Proportion of patients who die (global and by strata: serious and critical) according to their causes and treatment groups, during their stay at the CMN Siglo XXI Specialty Hospital). Measurement time: during hospital stay. 2) Need for invasive mechanical ventilation (orotracheal intubation) in critically ill patients and, time (in days) from intubation to weaning in critically ill (if applicable) and critical patients. Measurement time: During the stay in the COVID-19 internment area, until ventilatory weaning.

Key secondary outcomes:

1) Reduction in the deterioration of lung function (Proportion of patients who did not require an increase in FiO2 to keep SO2 stable and without the need for intubation and / or Percentage of patients who decreased positive pressure values at the end of expiration [PEEP] ). Measurement time: On the 7th day after starting the treatment. 2) Need and time (in days) of non-invasive mechanical ventilation and/or oxygen therapy. Measurement time: During the stay in the COVID-19 internment area. 3) Measurement of hyperinflammation score parameters (temperature, visceromegaly, cytopenias, triglycerides, aspartate aminotransferase - TGO, fibrinogen, ferritin, D-dimer). Measurement time: at the beginning, at 72 hours and on the 7th day after starting the treatment. 4) Stay (days) in the COVID-19 internment area and global hospita (Time from the inclusion in the trial, in the COVID-19 internment area, until discharge from said area, as well as the global time of stay in the hospital (from admission to discharge)). Measurement time: during the stay in the COVID-19 internment area and hospital in general. 5) Sequential organ failure evaluation (SOFA score). Measurement time: daily, during the stay in the COVID-19 internment area. 6) Immunological evaluation through the determination of pro and anti-inflammatory cytokines and chemokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF, IFN alpha, IFN gamma, CXCL8, CCL5, CXCL9 , CCL2, CXCL10) through multiple bead-based immunoassays, with quantification of Th1, Th2 and TH17 type cytokines, chemokines and IFN alpha in human serum. Measurement time: at the beginning, at 72 hours and on the 7th day after starting the treatment. 8) Behavior of biomarkers: absolute lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase - LDH, etc. Measurement time: at the beginning, 72 hours and 7th day after the start of treatment. 9) Antibody titers: IgM and IgG antibody titers against the S protein of the SARS-CoV-2 virus will be measured by ELISA. Measurement time: at the beginning, at 72 hours and on the 7th day after starting the treatment. 10) Cellular immunophenotype: It will be carried out through the analysis of cell populations by flow cytometry and confocal microscopy, using the markers: CD11c, MHC-II and BDCA-3, MDC-8, CD86, CD40, PDL-1, INF- α, TNF-α PD-1 and PD-L1, CTLA- and TIM-3 and IDO, CD103, CD69, CD44, CD62L CD3, CD4, CD8, INF-γ and granzyme B. Measurement time: at baseline, at 72 hours and on the 7th day after starting the treatment. 11) Imaging response: the evolution of pulmonary lesions will be evaluated by chest radiography, CT or pulmonary ultrasound. Measurement time: at the beginning, at 72 hours and on the 7th day after starting the treatment (and when clinically indicated). 12) Clinical Adverse Events-AE (They will be measured as: -Occurrence of AE (Yes, No), -Description of AE (name of event), -Intensity of AE (mild, moderate, severe), -Causality relationship (no related, doubtful, possible, probable, definitive), -Measures adopted (None, Administration of any pharmacological therapy, Addition of a non-pharmacological therapy, Study exit, Hospitalization / prolongation of hospitalization), -Result (Completely resolved, Resolved with sequelae, Conditions improving, Condition present and unchanged, Worsening, Death caused by this event)). Measurement time: daily during the entire period of admission to the COVID-19 internment area.

Selection criterias

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

Gender:

Male/Female

Minimum age:

18 years

Maximum age:

None

Inclusion criteria:

1) Patients aged ≥ 18 years. 2) Virological diagnosis by RT-PCR of infection to SARS-CoV-2. 3) Patients in serious or critical condition. 4) Acute respiratory failure according to clinical and Berlin criteria (imaging and oxygenation). 5) Voluntariness of the patient through informed consent.

Exclusion criteria:

1) Previous treatment with JAK inhibitor, tocilizumab or other anti-IL6R or IL-6, IL-1 inhibitor (Anakinra). 2) Patients with kidney disease on hemodialysis. 3) Patients who previously indicate NO intubation, NO resuscitation. 4) Known hypersensitivity to any of the components of the formulations under study. 5) Pregnancy or breastfeeding.

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:

2

Target sample size:

60

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:

Eduardo

Last Name:

Ferat Osorio

Specialty:

Medical Doctor

Affiliation:

Health Research Division. UMAE, Specialty Hospital Siglo XXI National Medical Center, IMSS.

Postal Address:

Avenida Cuauhtemoc # 330

City:

Mexico City

Country:

Mexico

Zip Code:

06720

Telephone:

+52-5556276900

Email :

eduardoferat@me.com

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; 1st and 2nd grade 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

Country:

Cuba

Zip Code:

11300

Telephone:

+53-72716022

Email :

hernandez.bernal@cigb.edu.cu

Research Ethics Committees

Section to complete the data related to the review ethics committees.

Name of Research Ethics Committees:

Instituto Mexicano del Seguro Social (IMSS)

Status of evaluation:

Approved

Status of evaluation date of Ethic Committee:

03/07/2020

Postal address of Ethic Committee :

Av. Cuauhtemoc 330, C.P. 06720, Mexico city, Mexico

Telephone:

+52-5556276900

Email:

-

About study completion

Section to complete the data related to the study completion.

Study completion date:

30/09/2020

Date of available results:

30/10/2020

Date of first publication:

30/11/2020

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:

RPCEC00000330

Date of Registration in Primary Registry:

11/08/2020

Record Verification Date:

2020/10/05

Next update date:

2021/10/05

Link to the spanish version:

Click here

Registered Trials

Registration process

DALIA Study

About the RPCEC

Useful resources