DOXYCOV: Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19

Sponsor

Yaounde Central Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04715295

Collaborator

(none)

200

Enrollment

Location

Arms

Anticipated Duration (Months)

18.2

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Oct 5, 2020

Anticipated Primary Completion Date :

May 30, 2021

Anticipated Study Completion Date :

Sep 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 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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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