Clinical trial NCT04715295: Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: COVID-19
Keywords: COVID-19
Doxycycline
Rivaroxaban
Hydroxychloroquine
Lead sponsor: Yaounde Central Hospital
Sponsor class: OTHER_GOV
First posted: 2021-01-20
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Clinical
timeFrame: Day 1 to 10
measure: Virological
timeFrame: Day 1 to 10
Secondary outcomes:
measure: Symptom remission
timeFrame: Day 1 to 10
measure: Hospitalisation
timeFrame: Day 1 to 10
measure: Mortality
timeFrame: Day 1 to 10
measure: Biological variables
timeFrame: Day 1 to Day 7 and Day 10
Other outcomes:
Locations:
city: Yaounde
country: Cameroon
facility: Yaounde Central Hospital
state: Centre
Study officials:
affiliation: University of Yaounde 1
name: Eugene Sobngwi
role: PRINCIPAL_INVESTIGATOR
References: