Evaluation of Prognostic Modification in COVID-19 Patients in Early Intervention Treatment

Covid19 Clinical Trial

Official title:

Prognostic Modification in Patients With COVID-19 Under Early Intervention Treatment at U.M.F 13 and U.M.F 20

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04673214
• Other study ID #: R-2020-785-176
• Status: Completed
• Phase: Phase 3
• Start date: December 16, 2020
• Est. completion date: February 25, 2021

Study information

• Verified date: August 2021
• Source: Coordinación de Investigación en Salud, Mexico
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The present study is designed for patients with mild COVID-19 phase, to demonstrate if there is a modification in the clinical evolution greater than or equal to 25% in their symptoms, implemented in two groups of patients under an early intervention treatment, a group ( A) will receive Azithromycin / Ivermectin / Ribaroxaban / Paracetamol and another group (B) will receive Azithromycin / Ribaroxaban / Paracetamol followed for 14 days followed by video call

Description:

Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potential fatal disease generating a global public health problem. Person-to-person transmission of COVID-19 infection led to the isolation of patients who subsequently received a variety of treatments. Ivermectin treatment for safety is approved for human use by the FDA in parasitic and skin infections. Studies report the therapeutic safety of Ivermectin in humans with COVID-19, describing a 6.1-fold decrease in lethality compared to patients who did not use Ivermectin (1.4 vs. 8.5%, p <0.0001). In this sense, the WHO and PAHO encourage the use of unproven therapies in the context of a randomized clinical trial (RCT). Anticoagulants have reported up to 20% in the reduction of mortality (heparin), Ribaroxaban is effective with the inhibition of PAR1 / PAR2 / PAR4 receptors through the blocking of Factor Xa and the formation of thrombin, having anti-inflammatory effects, decreasing arteriosclerosis and platelet aggregation. There is a Telemedicine working method implemented by the OOAD of the North Federal District, which detects early signs and symptoms of possible complications and offers an early intervention treatment policy for first-level care beneficiaries. Under this method, a quasi-experimental study showed that there is a modification in the frequency of recovered patients of 80-90% in patients diagnosed with COVID-19 after an early intervention treatment with paracetamol, Ivermectin, Azithromycin, Ribaroxaban in patients with COVID -19 from UMF 13 during the period of July-August 2020. Therefore, it is necessary to carry out a randomized clinical trial to confirm this assertion.

Objective: To evaluate the percentage of patients with a diagnosis of COVID-19 who modify their clinical evolution under a comparative treatment of early intervention in beneficiaries of the U.M.F 13 and U.M.F 20 of the I.M.S.S., during the period of December 2020-January 2021.

Material and Methods: A randomized, single-blind, prospective, longitudinal and open experimental study in 62 patients with COVID-19 from UMF No. 13 and No. 20 from November to December 2020. Including 31 patients in group A (Azithromycin / Ivermectin / Ribaroxaban / Paracetamol) and 31 patients in group B (Azithromycin / Ribaroxaban / Paracetamol). With inclusion criteria over 18 years of age, have type 2 diabetes mellitus, Systemic Arterial Hypertension, Obesity or overweight, PCR confirmation of COVID-19. For the video call, the Family Medicine Units have Electronic Equipment Installation for Internet use. Exclusion criteria are patients with severe COVID-19 (they deserve immediate referral to second level of care, hospital). Elimination criteria are Prior informed consent, medication is given randomly to a COVID-19 patient, a follow-up video call will be made at home for 14 days, recording sex, age, education, date of disease onset, taking laboratories (hematic biometry, C-reactive protein, D-dimer, Ferritin, prothrombin time, thromboplastin time, lactic dehydrogenase) taken at the onset of the disease, taking as an outcome variable the modification of the clinical course (clinical symptoms such as headache, cough, fever, conjunctivitis , myalgias, arthralgias, rhinorrhea, odynophagia, anosmia, chest pain, dyspnea) when granting treatment in groups A and B.. Statistical differences will be evaluated using the Mann-Whitney U test with a power of 90% and a type I error rate of 1% for the variable of modification of the clinical course in treatment groups A and B. analysis will be performed in SPSS version 21.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: February 25, 2021
• Est. primary completion date: February 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients Eligible for Family Medicine Unit No.20 and Family Medicine Unit No.13 belonging to the North DF of the IMSS.

• Male and female patients

• Patients over 18 years of age.

• Patients with compliance with the operational definition COVID-19 and confirmatory test of P.C.R. positive within the first days of the illness (that are evaluated in first level of medical attention).

• Patients with comorbidities such as Type 2 Diabetes Mellitus, Systemic Arterial Hypertension, Overweight or Obesity.

• That they agree to sign an informed consent

• Related to Video Call:

• That the Family Medicine Unit No.20 and the Family Medicine Unit No.13 belonging to the North DF of the IMSS have the Installation of Electronic Equipment for Internet use

Exclusion Criteria:

• Severe COVID-19 patients (Ameriten sent immediately to second level of care, hospital) Patients with any Personal Pathological History of Hematological Diseases. • Patients allergic to macrolides (Azithromycin) and Ivermectin.

Related Conditions & MeSH terms

• Covid19

Intervention

Drug:
• Azithromycin / Ivermectin / Ribaroxaban / Paracetamol
In the patient with the presence of COVID-19 confirmed by the PCR-COVID-19 positive test, the drug is randomly assigned to belong to group A of Azithromycin / Ivermectin / Ribaroxaban / Paracetamol to be followed for 14 days by video call (approximately 15 to 20 min per day) to the patient and the presence or absence of clinical symptoms, adverse reactions being recorded daily
• Azithromycin / Ribaroxaban / Paracetamol
In the patient with the presence of COVID-19 confirmed by the PCR-COVID-19 positive test, the drug is randomly assigned to belong to group B of Azithromycin / Ribaroxaban / Paracetamol, to be followed for 14 days by video call (approximately 15 to 20 min per day) to the patient and the presence or absence of clinical symptoms, adverse reactions being recorded daily

Locations

Country	Name	City	State
Mexico	Alma Italia Guerrero Martinez	Mexico	Distrito Federal

Sponsors (2)

Lead Sponsor	Collaborator
Gilberto Cruz Arteaga	Coordinación de Investigación en Salud, Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (6)

Arshad U, Pertinez H, Box H, Tatham L, Rajoli RKR, Curley P, Neary M, Sharp J, Liptrott NJ, Valentijn A, David C, Rannard SP, O'Neill PM, Aljayyoussi G, Pennington SH, Ward SA, Hill A, Back DJ, Khoo SH, Bray PG, Biagini GA, Owen A. Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics. Clin Pharmacol Ther. 2020 Oct;108(4):775-790. doi: 10.1002/cpt.1909. Epub 2020 Jun 14. Review. Erratum in: Clin Pharmacol Ther. 2021 May;109(5):1362. — View Citation

Becattini C, Pace U, Rondelli F, Delrio P, Ceccarelli G, Boncompagni M, Graziosi L, Visonà A, Chiari D, Avruscio G, Frasson S, Gussoni G, Biancafarina A, Camporese G, Donini A, Bucci AF, Agnelli G. Rivaroxaban for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer. Design of the PRO-LAPS II STUDY. Eur J Intern Med. 2020 Feb;72:53-59. doi: 10.1016/j.ejim.2019.11.015. Epub 2019 Dec 7. — View Citation

Choudhary R, Sharma AK. Potential use of hydroxychloroquine, ivermectin and azithromycin drugs in fighting COVID-19: trends, scope and relevance. New Microbes New Infect. 2020 Apr 22;35:100684. doi: 10.1016/j.nmni.2020.100684. eCollection 2020 May. Review. — View Citation

Dugina TN, Kiseleva EV, Chistov IV, Umarova BA, Strukova SM. Receptors of the PAR family as a link between blood coagulation and inflammation. Biochemistry (Mosc). 2002 Jan;67(1):65-74. Review. — View Citation

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20. — View Citation

Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, Streiff MB, Garcia DA, Liebman HA, Belani CP, O'Reilly EM, Patel JN, Yimer HA, Wildgoose P, Burton P, Vijapurkar U, Kaul S, Eikelboom J, McBane R, Bauer KA, Kuderer NM, Lyman GH; CASSINI Investigators. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. N Engl J Med. 2019 Feb 21;380(8):720-728. doi: 10.1056/NEJMoa1814630. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Average Days of COVID-19 Symptoms Under Treatment of Early Intervention Due to Outcome in UMF 13 and 20 of the IMSS	Statistical differences were evaluated using Student's t test for quantitative variables. The average duration of days with clinical symptoms of COVID-19 under early intervention treatment by outcome in the improvement of the modification of the clinical evolution of symptoms vs. therapeutic failure.	14 days
Other	Number of Participants Who Were Alive and Had COVID-19 Symptoms by Type of Therapy During a 14-day Follow-up	Survival analysis. The time it takes for 50% of COVID-19 patients to improve symptoms during a 14-day follow-up with dual therapy vs. triple therapy	14 days
Primary	Average Days in COVID-19 Symptoms by Type of Therapy in the UMF 20 and UMF 13 of the IMSS.	Statistical differences were evaluated using Student's t test for quantitative variables. In relation to the presence of the number of days with clinical symptoms of COVID-19 by double therapy vs. triple therapy.	14 days
Primary	Crosstabulated Outcome in Modification of the Evolution Clinical vs Fails Therapeutic by Type of Treatment in Patients With COVID-19 UMF 13 and UMF 20 of the IMSS	Statistical differences between clinical evolution vs therapeutic failure by type of treatment were evaluated using Pearson's Chi-square test as categorical variables.	14 days

External Links

•   Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management
•   Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial