COVID-19 trials registries data warehouse

https://www.isrctn.com/ISRCTN86534580

Emma Ogburn

principle@phc.ox.ac.uk

2020-03-22

Recruiting

RCT

Randomized

Parallel

Open label

single-center

Treatment

Current participant inclusion criteria as of 27/01/2022: 1. Participant or their legal representative, is willing and able to give informed consent for participation in the study, and is willing to comply with all trial procedures 2. A positive test for SARS-CoV-2 infection within the past 14 days (patient reported PCR test or lateral flow test result), with symptoms consistent with COVID-19* 3. Symptoms must have started within the past 14 days and be ongoing 4. Participant is aged 18 or over These symptoms may include, but are not limited to: a high temperature, a new, continuous cough, loss or change to your sense of smell or taste, sore throat, shortness of breath, general feeling of being unwell, muscle pain, diarrhoea and vomiting. Previous participant inclusion criteria as of 26/04/2021: 1. Participant is willing and able to give informed consent for participation in the study 2. Participant is willing to comply with all trial procedures 3. Suspected COVID-19 using the NHS syndromic definition, or symptoms consistent with COVID-19 (including, but are not limited to, shortness of breath, general feeling of being unwell, muscle pain, diarrhoea and vomiting) and with a positive test for SARS-CoV-2 infection within the past 14 days 4. Aged 65 years or over, aged 18-64 and is experiencing shortness of breath as part of COVID-19 illnesses, or aged 18-64 and has any of the following underlying health conditions: 4.1. Known weakened immune system due to a serious illness or medication (e.g. chemotherapy), 4.2. Known heart disease and/or a diagnosis of high blood pressure 4.3. Known chronic lung disease (e.g. asthma) 4.4. Known diabetes 4.5. Known mild hepatic impairment, 4.6. Known stroke or neurological problem, 4.7. Self-report obesity or body mass index =35 kg/m² Previous participant inclusion criteria as of 08/06/2020: 1. Participant is willing and able to give informed consent for participation in the study 2. Participant is willing to comply with all trial procedures 3. Onset of symptoms of possible COVID-19 in the community (continuous cough and/or high temperature) should be within 14 days of inclusion OR a positive test for SARS-Co-V2 infection which was taken fewer than 15 days ago, AND the participant is unwell with symptoms of COVID-19. These symptoms may include, but are not limited to, shortness of breath, general feeling of being unwell, muscle pain, diarrhoea, vomiting,fever and cough, and they must have had them for fewer than 15 days. 4. Patients aged =50-64 years with any of the following listed comorbidities OR patients aged =65 years with or without comorbidity: 4.1. Known weakened immune system due to serious illness or medication (e.g. chemotherapy) 4.2. Known heart disease and/or hypertension 4.3. Known asthma or lung disease 4.4. Known diabetes not treated with insulin 4.5. Known mild hepatic impairment 4.6. Known stroke or neurological problem _____ Previous inclusion criteria: 1. Participant is wil

Current participant exclusion criteria as of 27/01/2022: 1. Patient currently admitted in hospital 2. Almost recovered (generally much improved and symptoms now mild or almost absent) 3. Judgement of the recruiting clinician deems ineligible. 4. Previous randomisation to an arm of the PRINCIPLE trial 5. Known or suspected pregnancy 6. Breastfeeding 7. Women of childbearing potential (premenopausal female that is anatomically and physiologically capable of becoming pregnant*), or male with a partner of childbearing potential, not willing to use highly effective contraceptive** for the 28-day duration of the trial. As recorded by the participant on the screening form and confirmed on Day 1 by a call between clinician and participant * Highly effective methods have typical-use failure rates of less than 1% and include male or female sterilisation and long-acting reversible contraceptive (LARC) methods (intrauterine devices and implants) OR if a couple is using another method of contraception, such as a combined hormonal method, progestogen-only pill or injection, they are only eligible if they are willing to use an additional barrier method (e.g. male condom) for the 28-day duration of follow-up in the trial. Note: a barrier method on its own is not sufficient. Previous participant exclusion criteria as of 26/04/2021: 1. Patient currently admitted in hospital 2. Almost recovered (generally much improved and symptoms now mild or almost absent) 3. Judgement of the recruiting clinician deems ineligible 4. Previous randomisation to an arm of the PRINCIPLE trial Additional exclusion criteria specific to each intervention arm are listed in the Protocol. For participation, participants must be eligible to be randomised to at least one intervention arm as well as the Usual Care arm. Previous participant exclusion criteria as of 16/06/2020: 1. Patient currently admitted in hospital 2. Almost recovered (generally much improved and symptoms now mild or almost absent) 3. Judgement of the recruiting clinician deems ineligible 4. Patient already taking an intervention arm medication (hydroxychloroquine or azithromycin) or other macrolides or ketolides 5. Exclusion criteria related to azithromycin: 5.1. Pregnancy 5.2. Breastfeeding 5.3. Known severe hepatic impairment 5.4. Known severe renal impairment 5.5. Known myasthenia gravis 5.6. Previous adverse reaction to, or currently taking, azithromycin or other macrolides or ketolides 5.7. Patients taking the following drugs: hydroxychloroquine or chloroquine, sotalol, amiodarone, ciclosporin, digoxin, bromocriptine, cabergoline, ergotamine, ergometrine, methysergide or any ergot derivatives 5.8. Already taking antibiotics for an acute condition Known congenital or documented QT prolongation 5.9. Known allergy to soya or peanut due to the risk of hypersensitivity reactions _____ Previous exclusion criteria as of 08/06/2020: 1. Patient currently admitted in hos

2

University of Oxford

18

100

United Kingdom

Mild disease at enrollment

1: Mild disease at enrollment

12000

Current primary outcome measure as of 18/01/2021: The main objective of the trial is to assess the effectiveness of the interventions in reducing time to recovery and in reducing the incidence of hospitalisation and/or death.The trial has co-primary endpoints: 1. Time taken to self-reported recovery; defined as the first instance that a participant reports feeling recovered from possible COVID-19 2. Hospitalisation and/or death Both collected within 28 days of randomisation from patient report; study partner report; medical records; daily online symptom scores . _____ Previous primary outcome measure as of 10/06/2020: Hospital admission or mortality related to suspected COVID-19 infection assessed using reports of patients’ medical records; from enrolment up to 28 days after completing treatment _____ Previous primary outcome measure as of 08/06/2020: Hospital admission or mortality related to suspected COVID-19 infection. _____ Previous primary outcome measure: Hospital admission or death; for patients aged =50 years with comorbidity; and aged =65 years with or without comorbidity and suspected COVID-19 infection during time of prevalent COVID-19 infections; measured by hospital admission or mortality related to suspected COVID-19 within 28 days

Phase 3

[{"arm_notes": "", "treatment_id": 504, "treatment_name": "Favipiravir", "treatment_type": "Antivirals", "pharmacological_treatment": "Pharmacological treatment"}, {"arm_notes": "", "treatment_id": 693, "treatment_name": "Ivermectin", "treatment_type": "Antiparasitics", "pharmacological_treatment": "Pharmacological treatment"}]