Revisions for ESPERANZA study | Registro Público Cubano de Ensayos Clínicos

--- 17 April 2020 - 2:22pm by CIGB
+++ 17 April 2020 - 4:50pm by CIGB
-ESPERANSA study
+ESPERANZA study
-Patients with SARS-COVID-2 infection
+patients infected with the SARS-CoV-2 coronavirus.
-) Negativization of SARS-Cov-2 RNA in positive patients after starting antiviral therapy (time in days). Measurement time: At baseline, on the 2nd and on the 4th day (1st week) and in weeks 2, 3 and 4 after antiviral treatment.
+) Virological evaluation: Time until the negativity of the SARS-Cov-2 RNA (absence of the virus according to the qPCR technique in real time) in positive patients after starting antiviral therapy (the percentage of patients negative for SARS will be calculated). VOC-2 by qPCR in tissue of nasopharyngeal exudate Measurement time: 48, 72 and 96 hours after starting treatment.
-) Progression to severe COVID-19 (time in days). Measurement time: At baseline, on the 2nd and on the 4th day (1st week) and in weeks 2, 3 and 4 after antiviral treatment.
+) Clinical evaluation: Time to progression to severe COVID-19 (the percentage of patients who become severe will be calculated). Measurement time: 3rd week, after completion of the antiviral treatment under investigation.
-) COVID-19 mortality rate (numerical value). Measurement time: at week 4 after antiviral therapy.
+) Patients with unfavorable evolution (percentage of severe through clinical evaluations [fever, cough, dyspnea, etc.] and imaging (interstitial pneumonia by X-rays]). Measurement time: During the entire period of the study (three weeks).
-) Rate of deterioration of the patients reclassified as severe (numerical value): Measurement time: During the time of the study (4 weeks).
+) Increase in the levels of markers (at the RNA and serum levels) of response to IFNs (2-5OAS, Neopterin, β-2 microglobulin, Mx protein). The average value of the serum concentration measured by quantitative ELISA of 2´-5´OAS and Neopterin will be calculated. Measurement time: before starting treatment, and 7 and 14 days after starting treatment.
-) Full compliance with the therapeutic regimen and patient evaluations. Measurement time: At baseline, on the 2nd and on the 4th day (1st week) and in weeks 2, 3 and 4 after antiviral treatment.
+) Increased activation of the immune system (MHC-I / II expression, NK cells, cytotoxic T cells, macrophage activation). The percentage of activated cells will be calculated from the total number of patients who will receive treatment. Measurement time: before starting treatment, and 14 days after treatment.
-) Medication adjustment due to poor prognosis, severe adverse events, or death. Measurement time: During the studio execution time (4 weeks).
+) Clinical Adverse Events (AE). They will be measured as: -AE occurrence (Yes, No), -AE description (name of the event), -AE intensity (mild, moderate, severe), -Causal relationship (unrelated, doubtful, possible, probable, definitive), -Measures taken (None, Administration of some pharmacological therapy, Addition of a non-pharmacological therapy, Exit of the study, Hospitalization / prolongation of hospitalization), -Result (Fully resolved, Resolved with sequelae, Conditions in improvement, Present condition and unchanged, worsening, death caused by this event). Measurement time: daily throughout the study period (three weeks).
-) Clinical Adverse Events (AE). They will be measured as: -AE occurrence (Yes, No), -AE description (name of the event), -AE intensity (mild, moderate, severe), -Causal relationship (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 hospitalization), -Result (Fully resolved, Resolved with sequelae, Conditions in improvement, Present condition and unchanged, worsening, death caused by this event). Measurement time: At baseline, on the 2nd and on the 4th day (1st week) and in weeks 2, 3 and 4 after antiviral treatment.
-) Levels of markers (at the RNA and serum levels) of response to IFNs (2-5OAS, Neopterin, β-2 microglobulin, Mx protein). Measurement time: At the beginning, on the 2nd and on the 4th day (1st week) and in weeks 2, 3 and 4 after antiviral treatment.
-) Activation of the immune system (expression of MHC-I / II, NK cells, cytotoxic T cells, activation of macrophages). Measurement time: At baseline, on the 2nd and on the 4th day (1st week) and in weeks 2, 3 and 4 after antiviral treatment.
-Group I-Experimental: HeberFERON (Interferon alfa ganma recombinante)
+Group A: HeberFERON (Recombinant Interferon Alpha Gamma, 3.5 MUI), subcutaneously, twice a week for three consecutive weeks.
-HeberFERON (Interferon alfa ganma recombinante, 3.5 MIU), intramuscularly, 2-3 times per week for at least 3 consecutive weeks.
+Group B (Control): Heberon Alfa R (Recombinant Interferon alfa 2b, 3.0 MUI), subcutaneously, three times per week for three consecutive weeks.
-Group II-Experimental: Heberon Alfa R (Recombinant Interferon alfa 2b)
+All the patients included in the study (as part of the protocol of action foreseen in the country for cases of SARS-CoV-2 in nasopharyngeal exudates) receive basic treatment (in addition to interferon according to study group) with caletra, chloroquine, azithromycin or rocefin, depending on the magnitude of respiratory symptoms.
-Heberon Alfa R (Recombinant Interferon alfa 2b, 3.0 MIU), intramuscularly, 2-3 times per week for at least 3 consecutive weeks.
-) SARS-CoV-2 positive patients by rapid or confirmatory qPCR tests.
+) Positivity to SARS-CoV-2 by rapid or confirmatory test of qPCR.
-) Presence of any of the symptoms associated with the disease (fever, cough, dyspnea, interstitial changes in radiographic images) previous.
+) ECOG functional status ≤ 2 (Karnofsky ≥ 70%).
 ) Voluntariness of the patient by signing the informed consent.
-) Patients with decompensated chronic diseases, or autoimmune diseases.
+) Patients with decompensated chronic diseases at the time of inclusion (severe arterial hypertension, ischemic heart disease, diabetes mellitus, etc.).
-) Known hypersensitivity to any of the components of the formulation under study.
+) Patients with a history of autoimmune diseases.
-) Pregnancy or lactation.
+) Presence of hyperinflammation syndrome.
-) Obvious mental incapacity to issue consent and act accordingly with the study.
+) Serious coagulation disorders.
+) Known hypersensitivity to any of the components of the formulation under study.
+) Pregnancy or lactation.
+) Obvious mental incapacity to issue consent and act accordingly with the study.
-Uncontrolled
+Active
-/04/14
+/04/17
-/04/14
+/04/17
-Study of the administration of HeberFERON compared to Heberon Alfa R in patients with COVID-19.
+Evaluation of the effect and safety of HeberFERON versus Heberon alfa in patients infected with the SARS-CoV-2 coronavirus.

ESPERANZA 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 HeberFERON versus Heberon alfa in patients infected with the SARS-CoV-2 coronavirus.

Secondary indentifying numbers:

IG/IAG/CV/2001

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:

Idelsis

Last name:

Esquivel Moynelo

Medical Specialty :

Doctor in medicine. 1st degree specialist in Internal Medicine.

Affiliation:

Military Hospital "Dr. Luis Diaz Soto"

Postal address:

Ave Monumental 2 ½

City:

Havana

Country:

Cuba

Zip Code:

19130

Telephone:

+53-7680000

Email address:

idelsisem@infomed.sld.cu

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:

Not applicable

Recruitment status

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

Recruitment status:

Recruiting

Date of first enrollment:

10/04/2020

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:

patients infected with the SARS-CoV-2 coronavirus.

Intervention(s):

Group A: HeberFERON (Recombinant Interferon Alpha Gamma, 3.5 MUI), subcutaneously, twice a week for three consecutive weeks. Group B (Control): Heberon Alfa R (Recombinant Interferon alfa 2b, 3.0 MUI), subcutaneously, three times per week for three consecutive weeks. All the patients included in the study (as part of the protocol of action foreseen in the country for cases of SARS-CoV-2 in nasopharyngeal exudates) receive basic treatment (in addition to interferon according to study group) with caletra, chloroquine, azithromycin or rocefin, depending on the magnitude of respiratory symptoms.

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) Virological evaluation: Time until the negativity of the SARS-Cov-2 RNA (absence of the virus according to the qPCR technique in real time) in positive patients after starting antiviral therapy (the percentage of patients negative for SARS will be calculated). VOC-2 by qPCR in tissue of nasopharyngeal exudate Measurement time: 48, 72 and 96 hours after starting treatment. 2) Clinical evaluation: Time to progression to severe COVID-19 (the percentage of patients who become severe will be calculated). Measurement time: 3rd week, after completion of the antiviral treatment under investigation.

Key secondary outcomes:

1) Patients with unfavorable evolution (percentage of severe through clinical evaluations [fever, cough, dyspnea, etc.] and imaging (interstitial pneumonia by X-rays]). Measurement time: During the entire period of the study (three weeks). 2) Increase in the levels of markers (at the RNA and serum levels) of response to IFNs (2-5OAS, Neopterin, β-2 microglobulin, Mx protein). The average value of the serum concentration measured by quantitative ELISA of 2´-5´OAS and Neopterin will be calculated. Measurement time: before starting treatment, and 7 and 14 days after starting treatment. 3) Increased activation of the immune system (MHC-I / II expression, NK cells, cytotoxic T cells, macrophage activation). The percentage of activated cells will be calculated from the total number of patients who will receive treatment. Measurement time: before starting treatment, and 14 days after treatment. 4) Clinical Adverse Events (AE). They will be measured as: -AE occurrence (Yes, No), -AE description (name of the event), -AE intensity (mild, moderate, severe), -Causal relationship (unrelated, doubtful, possible, probable, definitive), -Measures taken (None, Administration of some pharmacological therapy, Addition of a non-pharmacological therapy, Exit of the study, Hospitalization / prolongation of hospitalization), -Result (Fully resolved, Resolved with sequelae, Conditions in improvement, Present condition and unchanged, worsening, death caused by this event). Measurement time: daily throughout the study period (three weeks).

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:

None

Inclusion criteria:

1) Positivity to SARS-CoV-2 by rapid or confirmatory test of qPCR. 2) ECOG functional status ≤ 2 (Karnofsky ≥ 70%). 3) Voluntariness of the patient by signing the informed consent.

Exclusion criteria:

1) Patients with decompensated chronic diseases at the time of inclusion (severe arterial hypertension, ischemic heart disease, diabetes mellitus, etc.). 2) Patients with a history of autoimmune diseases. 3) Presence of hyperinflammation syndrome. 4) Serious coagulation disorders. 5) Known hypersensitivity to any of the components of the formulation under study. 6) Pregnancy or lactation. 7) Obvious mental incapacity 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 trial

Masking:

Open

Control group:

Active

Study design:

Parallel

Phase:

Target sample size:

120

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:

Iraldo

Last Name:

Bello Rivero

Specialty:

Doctor in Biological Sciences

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

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

City:

La Habana

Country:

Cuba

Zip Code:

11300

Telephone:

+53-72085887, 72087465

Email :

iraldo.bello@cigb.edu.cu

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:

Iraldo

Last Name:

Bello Rivero

Specialty:

Doctor in Biological Sciences

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:

+53-72085887, 72087465

Email :

iraldo.bello@cigb.edu.cu

Research Ethics Committees

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

Name of Research Ethics Committees:

Military Hospital "Dr. Luis Díaz Soto"

Status of evaluation:

Approved

Status of evaluation date of Ethic Committee:

09/04/2020

Postal address of Ethic Committee :

Ave Monumental 2 ½, Habana del Este, La Habana, C.P:19130, Cuba

Telephone:

53-7680000

Email:

About study completion

Section to complete the data related to the study completion.

Final enrolment number:

Study completion date:

30/07/2020

Date of available results:

15/08/2020

Date of first publication:

31/08/2020

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:

RPCEC00000307

Date of Registration in Primary Registry:

14/04/2020

Record Verification Date:

2020/04/17

Next update date:

2021/04/17

Link to the spanish version:

Click here

Registered Trials

Registration process

ESPERANZA study

About the RPCEC

Useful resources