COVID-19
Conditions
Keywords
COVID-19, Doxycycline, Rivaroxaban, Hydroxychloroquine
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).
Interventions
Doxycycline 200 mg daily for 7 days
DRUGRivaroxaban 15Mg Tab
Rivaroxaban 15 mg tablets daily from day 1 to day 10
COMBINATION_PRODUCTHydroxychloroquine 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
Sponsors
Yaounde Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Cameroon
Contacts
Primary ContactEugene Sobngwi, MD, PhD
Backup ContactCharles Kouanfack, MD, PhD
Outcome results
None listed