Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19 (DOXYCOV)

• ClinicalTrials.gov Identifier: NCT04715295
• Recruitment Status: Recruiting
• First Posted: January 20, 2021
• Last Update Posted: January 20, 2021
• Sponsor: Yaounde Central Hospital
• Information provided by (Responsible Party): Sobngwi Eugene, Yaounde Central Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Doxycycline Tablets; Drug: Rivaroxaban 15Mg Tab; Combination Product: Hydroxychloroquine and Azithromycin	Phase 4

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Randomized Trial of the Safety and Efficacy of Doxycycline and Rivaroxaban Therapy Versus National Standard Therapy in Ambulatory Patients With Mild Symptomatic COVID-19
• Actual Study Start Date: October 5, 2020
• Estimated Primary Completion Date: May 30, 2021
• Estimated Study Completion Date: September 5, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Doxycyclin and Rivaroxaban; Oral Doxycyclin 200 mg daily for 7 days with or without Rivaroxaban	Drug: Doxycycline Tablets; Doxycycline 200 mg daily for 7 days; Other Name: Doxycycline; Drug: Rivaroxaban 15Mg Tab; Rivaroxaban 15 mg tablets daily from day 1 to day 10
Active Comparator: 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	Combination Product: 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

Outcome Measures

Primary Outcome Measures :

1. Clinical [ Time Frame: Day 1 to 10 ]
   Change of Clinical stage of COVID-19
2. Virological [ Time Frame: Day 1 to 10 ]
   Time to negativity of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) on nasopharyngeal swab.

Secondary Outcome Measures :

1. Symptom remission [ Time Frame: Day 1 to 10 ]
   Time to remission of symptoms in days
2. Hospitalisation [ Time Frame: Day 1 to 10 ]
   Need for hospitalisation due to worsening
3. Mortality [ Time Frame: Day 1 to 10 ]
   All-cause mortality
4. Biological variables [ Time Frame: Day 1 to Day 7 and Day 10 ]
   Change from baseline of WBC count

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Eugene Sobngwi, MD, PhD; +237675088750; sobngwieugene@yahoo.fr

Contact: Charles Kouanfack, MD, PhD

Locations

Cameroon

Yaounde Central Hospital; Recruiting

Yaounde, Centre, Cameroon

Sponsors and Collaborators

Yaounde Central Hospital

Investigators

• Principal Investigator: Eugene Sobngwi; University of Yaounde 1

More Information

• Responsible Party: Sobngwi Eugene, Medical Director, Yaounde Central Hospital
• ClinicalTrials.gov Identifier: NCT04715295
• Other Study ID Numbers: CNO0032020
• First Posted: January 20, 2021
• Last Update Posted: January 20, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data will be shared upon request and approval by the National COVID19 Scientific Board
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: one year after completion
• Access Criteria: Data will be shared upon request and approval by the National COVID19 Scientific Board

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Sobngwi Eugene, Yaounde Central Hospital:

COVID-19; Doxycycline; Rivaroxaban; Hydroxychloroquine

Additional relevant MeSH terms:

Azithromycin; Doxycycline; Hydroxychloroquine; Rivaroxaban; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Anticoagulants