Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19

NCT ID: NCT04715295

Last Updated: 2021-01-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-05
• Study Completion Date: 2021-09-05

Brief Summary

This is an exploratory study to evaluate the efficacy of Doxycycline (200mg on D1 to D7) and Rivaroxaban (15 mg daily on D1 to D7) versus the combination of Hydroxychloroquine (400 mg on D1 to D7) and Azithromycin (500 mg on D1 and 250mg on D2 to D5) as per national standard to treat ambulatory mild COVID-19 patients, with the aim to achieve early negativity of RT-PCR of SARS-CoV-2 from nasopharyngeal swab, and early clinical improvement and prevention of severe disease.

Detailed Description

This is an exploratory study to evaluate the efficacy of Doxycycline (200mg on D1 to D7) and Rivaroxaban (15 mg on D1 to D7) versus combination of hydroxychloroquine (400 mg on D1 to D7) and azithromycin (500 mg on D1 and 250mg on D2 to D5) to treat ambulatory patients with mild COVID-19.

We aim to demonstrate early improvement of a clinical core set of outcomes and prevention of clinical worsening, and early negativity of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) among ambulatory patients with mild COVID-19 by treating them with Doxycycline and Rivaroxaban compared to patients who receive Hydroxychloroquine and Azithromycin as per National standard therapy of COVid-19.

Ambulatory patients with mild symptoms and with confirmed diagnosis of COVID-19 will receive the treatment.

The primary objective of the study is to evaluate the Safety and Efficacy of Doxycycline and Rivaroxaban versus National standard therapy of mild COVid-19.

The primary endpoint is failure (i.e severe evolution) measured as PaO2 < 92% within 10 days after initiation of treatment.

The secondary objectives of the study are to evaluate

• Safety of the different investigational therapies up to D10 days of follow-up per arm,
• Hospitalisation due to Covid 19 infection rate per arm,
• Time to hospitalisation due to Covid 19 infection,
• Cure rate by treatment arm and Death rate,
• Worsening as assessed by the need for additional concomitant medication,
• Efficacy in sub-groups of patients (with pre-existing conditions/co-morbidities and by age group).

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Doxycyclin and Rivaroxaban

Oral Doxycyclin 200 mg daily for 7 days with or without Rivaroxaban

Group Type: EXPERIMENTAL

Doxycycline Tablets

Intervention Type: DRUG

Doxycycline 200 mg daily for 7 days

Rivaroxaban 15Mg Tab

Intervention Type: DRUG

Rivaroxaban 15 mg tablets daily from day 1 to day 10

National Standard

Hydroxychloroquine 400 mg daily for 5 days in combination with Azithromycin 500 mg on day 1 and 250 mg daily from day 2 through day 5

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine and Azithromycin

Intervention Type: COMBINATION_PRODUCT

Hydroxychloroquine 400mg daily from day 1 to day 5 in combination with Azithromycin 500mg on day 1 and 250 mg daily from day 2 to day 5

Interventions

Doxycycline Tablets

Doxycycline 200 mg daily for 7 days

Intervention Type: DRUG

Rivaroxaban 15Mg Tab

Rivaroxaban 15 mg tablets daily from day 1 to day 10

Intervention Type: DRUG

Hydroxychloroquine and Azithromycin

Hydroxychloroquine 400mg daily from day 1 to day 5 in combination with Azithromycin 500mg on day 1 and 250 mg daily from day 2 to day 5

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

Doxycycline

Eligibility Criteria

Inclusion Criteria

• COVID-19 infection confirmed by SARS-Cov2 - RT PCR - as per protocol
• Able to start the treatment within 24 hours from time of diagnosis
• Patient with mild symptoms as defined by WHO, with PaO2 > 93%
• Signed written consent of the patient
• Accepts and has the ability to be reached by phone during the study duration, plus a designated a contact person who can be contacted in case of emergency

Exclusion Criteria

• Blood pressure < 90/60mm Hg
• Respiratory rate ≥ 30/min
• Known cardiac condition
• Known G6PD deficiency
• Patients with < 45kg
• eGFR < 30 ml/min or ALT ≥ 3N or body temperature ≥ 38°C or any life-threatening comorbidity
• Any reason that makes it impossible to monitor the patient during the study period
• Baseline ECG prior to randomization showing QTc > 500 ms
• Ongoing treatment other than symptomatic
• history of retinopathy
• Absolute contra-indication to treatment with hydroxychloroquine (known hypersensitivity, concomitant treatment at risk of torsades de pointes)
• Contraindication to any study medication including allergy
• Ongoing treatment with high dose systemic chronic corticosteroid (> 40 mg)
• Patients treated by immunosuppressants treatment at the time of randomization
• Known Pregnant women and breastfeeding women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yaounde Central Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Sobngwi Eugene

Medical Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eugene Sobngwi

Role: PRINCIPAL_INVESTIGATOR

University of Yaounde 1

Locations

Yaounde Central Hospital

Yaoundé, Centre Region, Cameroon

Site Status: RECRUITING

Countries

Cameroon

Central Contacts

Eugene Sobngwi, MD, PhD

Role: CONTACT

sobngwieugene@yahoo.fr

+237675088750

Charles Kouanfack, MD, PhD

Role: CONTACT

References

Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.

Reference Type: DERIVED

PMID: 37591523 (View on PubMed)

Other Identifiers

CNO0032020

Identifier Type: -

Identifier Source: org_study_id