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

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

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.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Drug: Doxycycline Tablets; Drug: Rivaroxaban 15Mg Tab; Combination product: Hydroxychloroquine and Azithromycin

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 Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eugene Sobngwi, MD, PhD; Phone Number: +237675088750; Email: sobngwieugene@yahoo.fr
• Study Contact Backup: Name: Charles Kouanfack, MD, PhD

Study Locations

• Cameroon
  • Centre
    • Yaounde, Centre, Cameroon
      • Recruiting
      • Yaoundé Central Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom remission	Time to remission of symptoms in days	Day 1 to 10
Hospitalisation	Need for hospitalisation due to worsening	Day 1 to 10
Mortality	All-cause mortality	Day 1 to 10
Biological variables	Change from baseline of WBC count	Day 1 to Day 7 and Day 10

Collaborators and Investigators

• Sponsor: Yaounde Central Hospital
• Investigators: Principal Investigator: Eugene Sobngwi, University of Yaounde 1

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2020
• Primary Completion (Anticipated): May 30, 2021
• Study Completion (Anticipated): September 5, 2021

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 19, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Rivaroxaban; COVID-19; Hydroxychloroquine; Doxycycline
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Protease Inhibitors; Anti-Bacterial Agents; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Rivaroxaban; Doxycycline; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: CNO0032020

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• 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