Revisions for Therapy for COVID-19-Phase I-II | Registro Público Cubano de Ensayos Clínicos

--- 9 September 2020 - 1:21pm by SSA
+++ 9 September 2020 - 1:35pm by SSA
 Patients treated at home:
 Group I (experimental 1): Nebulization with Homeostec (5 ml) + Paracetamol (500 mg). The patient will receive a bottle with 5 ml of Homeostec (electrolysed solution with neutral pH), which will be placed in the nebulizer container. The patient will receive sprays for 15 min, four times a day for 7 days. In addition, you can take Paracetamol 500 mg (orally) every 6 hours.Other medications may be added at the discretion of the treating physician as deemed necessary for the patient.
-Group II (experimental 2): Nebulization with Homeostec (5 ml) + Paracetamol (500 mg) + Homeostec (15 ml, with dose escalation). The patient will receive a bottle with 5 ml of Homeostec (neutral pH electrolyzed solution), which will be placed in the nebulizer container. The patient will receive sprays for 15 min, four times a day for 7 days. Additionally, 15 ml of Homeostec will be administered intravenously loaded in a 20 ml syringe. The solution will be applied to an arm vein using a butterfly-type IV application catheter connected to the syringe, in a period of 1 to 2 min, once every 24 hours for 7 days, by research personnel who will visit the patient in his home. The initial intravenous dose of 15ml per day will have successive increments, before reaching dose-limiting toxicity, or until a dose was found that prevented disease progression. In addition, you can take Paracetamol 500 mg (orally) every 6 hours. Other medications may be added at the discretion of the treating physician as deemed necessary for the patient.
+Group II (experimental 2): Nebulization with Homeostec (5 ml) + Paracetamol (500 mg) + Homeostec  intravenously (15 ml, with dose escalation). The patient will receive a bottle with 5 ml of Homeostec (neutral pH electrolyzed solution), which will be placed in the nebulizer container. The patient will receive sprays for 15 min, four times a day for 7 days. Additionally, 15 ml of Homeostec will be administered intravenously loaded in a 20 ml syringe. The solution will be applied to an arm vein using a butterfly-type IV application catheter connected to the syringe, in a period of 1 to 2 min, once every 24 hours for 7 days, by research personnel who will visit the patient in his home. The initial intravenous dose of 15ml per day will have successive increments, before reaching dose-limiting toxicity, or until a dose was found that prevented disease progression. In addition, you can take Paracetamol 500 mg (orally) every 6 hours. Other medications may be added at the discretion of the treating physician as deemed necessary for the patient.
 Group III (control 1, usual medical care): Paracetamol (500 mg). The patient will receive Paracetamol 500 mg (orally) every 6 hours. Other medications may be added at the discretion of the treating physician as deemed necessary for the patient.
 For group I and II: If there is nausea, vomiting and / or diarrhea, 30 ml of oral Homeostec is added, 4 times a day, for as long as symptoms lasted, plus 2 more days after symptoms disappeared. In patients with oropharyngeal ulcerations (causing intense throat pain), the indication is to gargle with 10 ml of Homeostec, 6 times a day, and swallow the solution after gargling with it. This is done for the number of days necessary for the pain to decrease
+On August 28, the report with the first results of the clinical trial was submitted to the journal BMC Infectious Diseases. As of September 9, the status of the manuscript is "Editorial Assessment", hoping to move to the review phase soon. Until today, September 9, there are data on the effect of the experimental treatment on “Patients treated at home”, of which the results are mentioned below.
+Participant flow: Ninety-eight patients were randomized and screened. A total of 45 patients in the experimental group (experimental 1 + 2 groups) and 39 patients in the control group agreed to participate in the study, completed it, and were analyzed
+Baseline characteristics: 39 patients were included in Group III (control 1, usual medical care); 45 patients in Groups I and II (experimental groups 1 and 2). Control vs Experimetal groups: Women: 46.2% vs 46.7% (p = 0.568); Age (years) 46 ± 16.3 vs 48 ± 12.9 (P = 0.512); BMI: 30.1 ± 4.4 vs 28.9 ± 4.6 (P = 0.256); Diabetes: 12.8% vs 11.1% (0.536); High blood pressure: 17.9% vs 20.0% (P = 0.517); Smoking: 2.6% vs 8.9% (P = 0.228); Progression time in days: 4.1 ± 1.6 vs 4.8 ± 3.4 (P = 0.196); Patient overall self-assessment or symptom severity score (self-assessed using a 10-point VAS): 7.0 ± 3.0 vs 6.3 ± 2.3 (P = 0.244).
+Outcome measures: Disease progression (present or absent). In the control group, 30.8% of the patients had disease progression (hospitalization), compared with 11.1% of the patients receiving the experimental therapy (P = 0.020). 12.8% of the patients in the control group died, while no patients in the experimental groups died (P = 0.019). Control group patients reached an acceptable state of their symptoms (median) on day 11, patients in experimental group 1 (Nebulization with Homeostec + Paracetamol) recovered on day 7, and the highest dose tested in experimental group 2 ( Nebulization with Homeostec + Homeostec intravenously, with dose escalation) was on day 2. The highest doses of Homeostec intravenously were 30ml / day and 30ml every 12 hours, for 7 days.
+Adverse events: No serious adverse events were found by the administration of Homeostec. Some mild events did occur: 1 patient did not tolerate nebulizations and discontinued them on day 2. Two patients reported transitory dizziness lasting for 10 min, after the intravenous application of the experimental solution. It was self-limited and controlled by lying down. There were no alterations in blood cell parameters, serum biochemical tests of liver and kidney function.
+The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.

Therapy for COVID-19-Phase I-II

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.

Acronym of Public Title:

TX-COVID19

Scientific title:

Evaluation of the effect of 0.002% sodium chloride saline (activated) administered intravenously and / or mists in patients with covid-19. (COVID-19)

Acronym of Scientific Title:

TX-COVID19

Secondary indentifying numbers:

Not applicable.

Issuing authority of the secondary identifying numbers:

Not applicable.

Source(s) of monetary or material support:

1) Cancerology State Institute, Colima State Health Service (SSA-Colima), Mexico. 2) Medical School of the University of Colima, Mexico.

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:

Only approved by Ethics Committees

Principal investigator

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

First name:

Ivan

Last name:

Delgado Enciso

Medical Specialty :

General Medicine. Specialist in Molecular Biology

Affiliation:

Cancerology State Institute, Colima State Health Service, Mexico.

Postal address:

Avenue Liceo de Varones 401, Colonia La Esperanza.

City:

Colima

Country:

Mexico

Zip Code:

28085

Telephone:

+52-3121521435

Email address:

ivan_delgado_enciso@ucol.mx

ivancoliman@hotmail.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:

Recruiting

Date of first enrollment:

20/05/2020

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

Health condition(s) code:

Coronavirus Infections

SARS Virus

Coronaviridae Infections

Betacoronavirus

Health condition keyword:

SARS-CoV-2

covid-19

Intervention(s):

Patients treated at home: Group I (experimental 1): Nebulization with Homeostec (5 ml) + Paracetamol (500 mg). The patient will receive a bottle with 5 ml of Homeostec (electrolysed solution with neutral pH), which will be placed in the nebulizer container. The patient will receive sprays for 15 min, four times a day for 7 days. In addition, you can take Paracetamol 500 mg (orally) every 6 hours.Other medications may be added at the discretion of the treating physician as deemed necessary for the patient. Group II (experimental 2): Nebulization with Homeostec (5 ml) + Paracetamol (500 mg) + Homeostec intravenously (15 ml, with dose escalation). The patient will receive a bottle with 5 ml of Homeostec (neutral pH electrolyzed solution), which will be placed in the nebulizer container. The patient will receive sprays for 15 min, four times a day for 7 days. Additionally, 15 ml of Homeostec will be administered intravenously loaded in a 20 ml syringe. The solution will be applied to an arm vein using a butterfly-type IV application catheter connected to the syringe, in a period of 1 to 2 min, once every 24 hours for 7 days, by research personnel who will visit the patient in his home. The initial intravenous dose of 15ml per day will have successive increments, before reaching dose-limiting toxicity, or until a dose was found that prevented disease progression. In addition, you can take Paracetamol 500 mg (orally) every 6 hours. Other medications may be added at the discretion of the treating physician as deemed necessary for the patient. Group III (control 1, usual medical care): Paracetamol (500 mg). The patient will receive Paracetamol 500 mg (orally) every 6 hours. Other medications may be added at the discretion of the treating physician as deemed necessary for the patient. For group I and II: If there is nausea, vomiting and / or diarrhea, 30 ml of oral Homeostec is added, 4 times a day, for as long as symptoms lasted, plus 2 more days after symptoms disappeared. In patients with oropharyngeal ulcerations (causing intense throat pain), the indication is to gargle with 10 ml of Homeostec, 6 times a day, and swallow the solution after gargling with it. This is done for the number of days necessary for the pain to decrease Hospitalized patients (Includes patients on a regular floor or intensive care unit, with or without mechanical ventilation): Group IV (experimental 3): Homeostec (15 ml, with dose escalation) + Paracetamol (500 mg). The patient will receive 15 ml of Homeostec (pH neutral electrolyzed solution) intravenously loaded into a 20 ml syringe. The solution will be applied via a butterfly-type IV application catheter connected to the syringe, within 1 to 2 min once every 12 hours for 7 days. In addition, you can take Paracetamol 500 mg (orally) every 6 hours. Other medications may be added at the discretion of the treating physician as deemed necessary for the patient. Group V (control 2): 0.9% physiological solution (15 ml) + Paracetamol (500 mg). The patient will receive 15 ml of 0.9% Physiological Solution intravenously loaded into a 20 ml syringe. The solution will be applied via a butterfly-type IV application catheter connected to the syringe, within 1 to 2 min once every 12 hours for 7 days. In addition, you will receive paracetamol 500 mg (orally) every 6 hours. Other medications may be added at the discretion of the treating physician as deemed necessary for the patient.

Intervention code:

Saline Solution

Acetaminophen

Tablets

Administration, Intravenous

Administration, Oral

Administration, Inhalation

Intervention keyword:

Homeostec, Paracetamol

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):

Disease progression (present or absent). Measurement time: Daily until 14th day. Patients treated at home. The progression will be present when hospitalization or death occurs. In hospitalized patients: The progression will be present when they are in the usual hospital floor and without a ventilator, progression is considered when there is death or admission to the Intensive Care Unit (ICU) or requiring mechanical ventilation. Patients enrolled in the trial after admission to the ICU or already on mechanical ventilation. The progression will be present when death occurred.

Key secondary outcomes:

Adverse Events-AE (Present or Absent. AE will be classified according to the "Common Terminology Criteria for Adverse Events (CTCAE) version 5). Measurement time: Daily until 14th day. Change in laboratory test values (Dimero D, C-reactive protein, fibrinogen and erythrocyte sedimentation rate). Measurement time: Basal, at 2, 4, 6 and 14 days.

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:

75 years.

Inclusion criteria:

A) For outpatients treated at home (without pneumonia and with peripheral blood oxygen saturation equal to or greater than 90% breathing ambient air): 1. Patients diagnosed with COVID-19, with uncomplicated disease. 2. Age: 18 years - 75 years old. 3. Acceptance in writing, with prior information. B) For hospitalized patients (with pneumonia or peripheral blood oxygen saturation less than 90% breathing ambient air or requiring mechanical ventilation): 1. Patients diagnosed with COVID-19, with mild or severe pneumonia hospitalized. 2. Age: 18 years - 75 years old. 3. Acceptance in writing, with prior information.

Exclusion criteria:

FOR ALL PATIENTS 1. Rheumatoid arthritis. 2. Autoimmune diseases. 3. Previously diagnosed cardiac diseases (ischemic). 4. Chronic decompensated systemic disease prior to the diagnosis of COVID-19. 5. Creatinine 1.25 times higher than the normal value or creatinine clearance less than 50 milliliters / minute (Cockfrot and Gault method), prior to the diagnosis of COVID-19. 6. Blood hemoglobin less than 10g / Dl, prior to the diagnosis of COVID-19. 7. Increase in the last month of diastolic blood pressure to 110 mmHg or more and / or appearance of hematuria or proteinuria greater than 300 milligrams / day. 8. Intestinal pseudo-obstruction. Defined as abdominal pain, with airborne levels on radiographs of the AP abdomen and lateral foot. 9. Pregnant and lactating women. 10. Drug addiction (illicit drugs). 11. Known liver disease prior to the diagnosis of COVID-19 with a doubling of liver function tests (Aspartatoamine transferase (AST), Alaninoamine transferase (ALT), Alkaline phosphatase, Bilirubins). 12. Presence of Cancer. 13. Other pathologies at the discretion of the researcher.

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:

1-2

Target sample size:

100

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:

Juan

Last Name:

Paz Garcia

Specialty:

Maxillofacial Surgery.

Affiliation:

Cancerology State Institute, Colima State Health Service, Mexico. Voluntary.

Postal Address:

Avenue Liceo de Varones 401, Colonia La Esperanza.

City:

Colima

Country:

Mexico

Zip Code:

28950

Telephone:

+52-3123195722

Email :

dr_juanpaz@hotmail.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:

Ivan

Last Name:

Delgado Enciso

Specialty:

General Medicine. Specialist in Molecular Biology

Affiliation:

Cancerology State Institute, Colima State Health Service, Mexico.

Postal Address:

Avenue Liceo de Varones 401, Colonia La Esperanza.

City:

Colima

Country:

Mexico

Zip Code:

28085

Telephone:

+52 3121521435

Email :

ivan_delgado_enciso@ucol.mx

ivancoliman@hotmail.com

Research Ethics Committees

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

Name of Research Ethics Committees:

Comite de Bioetica de la Facultad de Medicina de la Universidad de Colima

Status of evaluation:

Approved

Status of evaluation date of Ethic Committee:

08/04/2020

Postal address of Ethic Committee :

Avenida Universidad 333, Colonia Las Viboras, C.P. 28040 Colima, Mexico

Telephone:

+52312316-1099 ext. 37501

Email:

medicina@ucol.mx; fespin@ucol.mx

About study completion

Section to complete the data related to the study completion.

Study completion date:

15/01/2021

Date of available results:

16/07/2021

Date of first publication:

01/12/2021

Results Study

Section to complete the data related to the summarized results.

Summary study:

On August 28, the report with the first results of the clinical trial was submitted to the journal BMC Infectious Diseases. As of September 9, the status of the manuscript is "Editorial Assessment", hoping to move to the review phase soon. Until today, September 9, there are data on the effect of the experimental treatment on “Patients treated at home”, of which the results are mentioned below. Participant flow: Ninety-eight patients were randomized and screened. A total of 45 patients in the experimental group (experimental 1 + 2 groups) and 39 patients in the control group agreed to participate in the study, completed it, and were analyzed Baseline characteristics: 39 patients were included in Group III (control 1, usual medical care); 45 patients in Groups I and II (experimental groups 1 and 2). Control vs Experimetal groups: Women: 46.2% vs 46.7% (p = 0.568); Age (years) 46 ± 16.3 vs 48 ± 12.9 (P = 0.512); BMI: 30.1 ± 4.4 vs 28.9 ± 4.6 (P = 0.256); Diabetes: 12.8% vs 11.1% (0.536); High blood pressure: 17.9% vs 20.0% (P = 0.517); Smoking: 2.6% vs 8.9% (P = 0.228); Progression time in days: 4.1 ± 1.6 vs 4.8 ± 3.4 (P = 0.196); Patient overall self-assessment or symptom severity score (self-assessed using a 10-point VAS): 7.0 ± 3.0 vs 6.3 ± 2.3 (P = 0.244). Outcome measures: Disease progression (present or absent). In the control group, 30.8% of the patients had disease progression (hospitalization), compared with 11.1% of the patients receiving the experimental therapy (P = 0.020). 12.8% of the patients in the control group died, while no patients in the experimental groups died (P = 0.019). Control group patients reached an acceptable state of their symptoms (median) on day 11, patients in experimental group 1 (Nebulization with Homeostec + Paracetamol) recovered on day 7, and the highest dose tested in experimental group 2 ( Nebulization with Homeostec + Homeostec intravenously, with dose escalation) was on day 2. The highest doses of Homeostec intravenously were 30ml / day and 30ml every 12 hours, for 7 days. Adverse events: No serious adverse events were found by the administration of Homeostec. Some mild events did occur: 1 patient did not tolerate nebulizations and discontinued them on day 2. Two patients reported transitory dizziness lasting for 10 min, after the intravenous application of the experimental solution. It was self-limited and controlled by lying down. There were no alterations in blood cell parameters, serum biochemical tests of liver and kidney function. The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.

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:

RPCEC00000309

Date of Registration in Primary Registry:

05/05/2020

Record Verification Date:

2020/09/09

Next update date:

2021/09/09

Link to the spanish version:

Click here

Registered Trials

Registration process

Therapy for COVID-19-Phase I-II

About the RPCEC

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