Revisions for Itolizumab-Plasmapheresis in patients with COVID-19 | Registro Público Cubano de Ensayos Clínicos

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Revision of 7 July 2021 - 10:42am:

Itolizumab-Plasmapheresis in patients with COVID-19

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:

Therapeutic proposal of plasmapheresis and the anti-CD6 monoclonal antibody Itolizumab in the treatment of patients with COVID-19. (COVID-19)

Secondary indentifying numbers:

In process

Issuing authority of the secondary identifying numbers:

Center of Molecular Immunology (CIM)

Source(s) of monetary or material support:

Center of Molecular Immunology (CIM), Cuban Ministry of Public Health (MINSAP)

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:

Idamis

Last name:

Fernandez Jure

Medical Specialty :

First Degree Specialist in General Medicine . Master in Infectious Diseases

Affiliation:

Provincial Blood Bank of Villa Clara

Postal address:

Maceo street 368 between Nazareno and Sindico

City:

Santa Clara

Country:

Cuba

Zip Code:

50100

Telephone:

+53-42207736

Email address:

jure@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:

Villa Clara, "Manuel Fajardo Rivero" Hospital, Carlos Hidalgo Mesa HD, Second Degree Specialist in Internal Medicine

Recruitment status

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

Recruitment status:

Pending

Date of first enrollment:

27/09/2021

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

Health condition(s) code:

Coronavirus Infections

SARS Virus

Coronaviridae Infections

Nidovirales Infections

Betacoronavirus

Health condition keyword:

COVID-19

SARS-CoV2

Intervention(s):

Itolizumab (Experimental Group): Itolizumab + Plasmapheresis Itolizumab: A first dose of Itolizumab (humanized anti-CD6 monoclonal antibody) 1.6 mg / kg will be administered by intravenous route. In case the patient, because of its body weight (≥125 kg), requires more than 200 mg according to the proposed dose, only 200 mg will be administered. if the patient is no improvement in the symptoms and signs of the systemic inflammatory disease, the patient can receive additional doses of itolizumab up to a maximum of 4 doses, with intervals of 3 to 7 days after the preceding dose, for a maximum of 28 days. Plasmapheresis: It will be performed by intravenous route through the ulnar or lateral vein of the elbow flexure, with Cuff Pressure of 50mm Hg, using a Haemonetics or Nigale machine. It can be performed initially, concurrent with the administration of the first dose of Itolizumab; or the relevance of its use can be evaluated, 72 hours after the first dose of Itolizumab has been administered, taking into account the clinical status of the patient and the values of the laboratory parameters, especially the neutrophil / lymphocyte ratio (NLR). Plasmapheresis will be performed immediately before the administration of the corresponding Itolizumab dose. Up to a maximun of 4 plasmapheresis sessions can be performed.

Intervention code:

Antibodies, Monoclonal, Humanized

Antibodies, Monoclonal

Plasmapheresis

Infusions, Intravenous

Intervention keyword:

Itolizumab

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- Recovery rate (The proportion of patients considered recovered will be calculated in relation to the total number of patients who received the therapeutic combination). Measurement time: At hospital discharge. 2- Rate of patients with disease progression (worsening in the classification of clinical status. According to the World Health Organization classification of Moderate, Severe, Critical (Stable, Unstable), any change in status during the evaluation period will be considered Progression). Measurement time: from the first plasmapheresis session at 0, 48h, 72h, 120h, 168h, 14 days, 21 days and 28 days or until hospital discharge or death of the patient.

Key secondary outcomes:

1- Intensive care stay time (Time elapsed from admission until discharge from the ICU). Measurement time: At ICU discharge 2- Hospital stay time (Time elapsed from hospital admission until to hospital discharge). Measurement time: At hospital discharge. Lung function: 3- Rate of patients without the need to increase FiO2 to keep SO2 stable (Proportion of patients in whom it is not necessary to increase FiO2). Measurement time: At hospital discharge. 4- Rate of patients who improve the PO2/FiO2 ratio (Rate of patients who increase the PO2/FiO2 ratio). Measurement time: At hospital discharge. 5- Rate of patients requiring non-invasive mechanical ventilation-NIMV (Rate of patients requiring non-invasive mechanical ventilation after starting treatment with the therapeutic combination). Measurement time: At hospital discharge. 6- Rate of patients requiring invasive mechanical ventilation (Rate of patients requiring invasive mechanical ventilation after starting treatment with the therapeutic combination). Measurement time: At hospital discharge. 7- Clinical Adverse Events-AE (From the total number of patients who will receive the therapeutic combination, the percentage that developed serious AE will be calculated, according to the CTCAE v5.0 classification. The type, duration, severity, result and causal relationship of the AE will be recorded). Measurement time: After each dose of therapeutic combination has been administered and during the entire hospitalization period and until hospital discharge. 8- Inflammation Markers (Evaluation of serum concentrations of IL6, Interferon gamma, TNF alpha and Neutrophil / lymphocyte ratio (NLR)). Measurement time: before each plasmapheresis session, immediately after plasmapheresis and 72 hours after plasmapheresis, and up to 72 hours after the last plasmapheresis. 9- Clinical laboratory tests (Evaluation of concentrations of Hemoglobin (Hb), Total leukocytes, Neutrophils, Lymphocytes, Platelets, Erythrosedimentation, C-reactive protein, Triglycerides, Ferritin, Creatinine, LDH (Lactate dehydrogenase), Amino-aspartate transferase, Pyruvic glutamic transferase, Fibrinogen, D-Dimer). Measurement time: before each plasmapheresis session, immediately after plasmapheresis and 72 hours after plasmapheresis, until discharge from hospital.

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. Express voluntariness of the patient, family member or impartial witness. 2. Any gender and skin color 3. Patients 18 years of age and older 4. SARS-CoV-2 infection diagnosed by RT-PCR categorized as moderate high risk or severe and critical patients, presenting any of the following characteristics: - Confirmed multifocal interstitial pneumonia or, - Need for oxygen therapy to maintain SO2> 93% or; - Worsening of lung involvement, defined as one of the following criteria: - Worsening of oxygen saturation> 3 percentage points or decrease in PaO2> 10%, with stable FiO2 in the last 24h. -Need to increase FiO2 in order to maintain a stable SO2 or new need for mechanical installation in the last 24 hours. - Increase in the number and / or extent of lung areas of consolidation. For confirmed cases RT-PCR positive SYMPTOMATIC RT-PCR positive "Moderate high risk". Patients with manifestations of infection 1-lower respiratory tract WITHOUT signs of severity (mild pneumonia) that are: 2-Patients 65 years of age or older; or 3- Patients who have any of the risk factors associated with mortality in COVID-19 (obesity, complicated HT, ischemic heart disease, diabetes mellitus, COPD, cancer, kidney failure, severe malnutrition, neutrophil / lymphocyte ratio> 4 and others that consider the attending physicians). Important: These cases will be treated in a different room with the supervision of the intensivists. Each case will be evaluated individually (if the disease has been evolving for 8 days or more, treatment with Heberferon should be suspended, and prophylactic anticoagulant treatment should be indicated in cases that meet the criteria for said therapy). 5. Alternatively, Itolizumab can be used in patients with suspected macrophage activation syndrome, according to the following criteria: Need for oxygen therapy not less than 6L / min plus one of the following conditions: • Wheezing or choppy speech (cannot quickly count to 20 after a deep breath) • Respiratory rate greater than 22 breaths per minute with oxygen therapy at 6L / min • PO2: Partial pressure of arterial oxygen <65 mm Hg • Worsening of the radiological image • Fever ≥38ºC • Reduction in baseline hemoglobin, platelets or neutrophils oHb <90 g / L, platelets <100 x109 / L, neutrophils <1 x109 / L or leukocytes <4 x109 / L. • Decrease in erythrocyte sedimentation in disagreement with C-reactive protein (pcr) (low erythrocyte sedimentation and CRP increases or does not change) • Increase in the initial value of triglycerides or triglycerides greater than 3 mmol. / L. • Increase in the initial value of ferritin from 500 ng / ml or absolute value of ferritin ≥ 2000 ng / ml. • Aspartate aminotransferase transaminase ≥30 IU / L • Increase in D-dimer • Fibrinogen <2.5 g / L • Appearance of neurological manifestations. In addition, they must meet the specific criteria for the execution of the plasmapheresis procedure; 6. Weight of the patient more than 57 kg and height greater than 1.10 m. 7. Moderate patients at high risk, whose clinical and laboratory manifestations worsen. 8. Neutrophil / lymphocyte ratio> 5, whether or not Itolizumab has been administered 9. Coagulation test: Clotting time (5 to 11 minutes)

Exclusion criteria:

1. Pregnant or lactating women. 2. Patients under 18 years of age. 3. Patients with hypercoagulation 4. Cancer patients 5. Patients with severe malnutrition, uncontrolled heart disease, patients previously subjected to cardiovascular surgery, with peptic ulcers or upper or lower limb amputation.

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:

N/A: single arm study

Masking:

Open

Control group:

Historical

Study design:

Single group

Phase:

N/A

Target sample size:

50

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:

Geidy

Last Name:

Lorenzo Monteagudo

Specialty:

BSc. in Pharmaceutical Sciences, Master in Toxicology

Affiliation:

Center of Molecular Immunology (CIM)

Postal Address:

216 street corner 15, Atabey, Playa, Box11600

City:

Havana

Country:

Cuba

Zip Code:

16040

Telephone:

+53-53806987

Email :

geydi@cim.sld.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:

Idamis

Last Name:

Fernandez Jure

Specialty:

First Degree Specialist in General Medicine. Master in Infectious Diseases

Affiliation:

Provincial Blood Bank of Villa Clara

Postal Address:

Maceo street 368 between Nazareno and Sindico

City:

Santa Clara

Country:

Cuba

Zip Code:

50100

Telephone:

+53-42207736

Email :

jure@infomed.sld.cu

Research Ethics Committees

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

Name of Research Ethics Committees:

"Manuel Fajardo Rivero" Military Hospital

Status of evaluation:

Approved

Status of evaluation date of Ethic Committee:

18/03/2021

Postal address of Ethic Committee :

Abel Santa Maria. Santa Clara, Villa Clara. ZC 50100, Cuba

Telephone:

+53-42206064

Email:

hadier@infomed.sld.cu

About study completion

Section to complete the data related to the study completion.

Study completion date:

27/06/2022

Date of available results:

31/10/2022

Date of first publication:

31/12/2022

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:

RPCEC00000380

Date of Registration in Primary Registry:

30/06/2021

Record Verification Date:

2021/07/07

Next update date:

2022/07/07

Link to the spanish version:

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Registered Trials

Registration process

Itolizumab-Plasmapheresis in patients with COVID-19

About the RPCEC

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