Clinical trial NCT04703608: Prevention and Treatment for COVID -19 (Severe Acute Respiratory Syndrome Coronavirus 2 SARS-CoV-2) Associated Severe Pneumonia in the Gambia
Official title: Prevention and Treatment for COVID -19 Associated Severe Pneumonia in The Gambia: a Single-Blinded Randomised Clinical Trial (PaTS-COVID)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Covid-19
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
First posted: 2021-01-11
Enrollment: 1200
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two cohorts study as follows:

* Cohort 1: intervention with Ivermectin
* Cohort 2: intervention with Aspirin Parallel assignment
Primary purpose: TREATMENT

Brief summary: The trial aims to assess the impact of cheap, licenced and widely available investigational products on the natural history of SARS-CoV-2 infection in 2 groups of patients - those with mild or moderate pneumonia (Cohort 1) and those with severe pneumonia (Cohort 2), through randomisation to non-identical placebo or intervention arm.

Detailed description: The trial is adaptive in design, with the option to change the investigational products should evidence change on the benefits/harms of the interventions being trialed.

Cohort 1. Currently index cases with mild COVID-19 or moderate pneumonia will be randomized to ivermectin 0.3-0.4mg/Kg daily for 3 days (arms 1 and 2) or non-identical placebo (arm 3). Index case randomization will also include HH members who will be treated with ivermectin 0.3-0.4mg/Kg daily for 3 days (arm 1) or non-identical placebo (arms 2 and 3). All households will receive a preventative package (containing soap, bleach, cloth facemasks and instructions on their use).

Cohort 2. Patients admitted to hospital meeting WHO criteria for severe COVID-19 pneumonia will be randomized to aspirin 150mg daily or non-identical placebo for 28 days or until hospital discharge (whichever is sooner). Other care will follow National guidelines.

The study will be conducted at multiple sites in The Gambia, with the option to recruit from other West African countries should this be necessary (subject to further local ethical review/s).

Eligibility criteria: Inclusion Criteria:

* Cohort 1:

Index case - Individuals ≥ 5 years of age with confirmed COVID19 mild disease or moderate pneumonia defined as:

* Mild disease - Influenza like illness, with any of the following symptoms cough, fever, headache, sore throat, nasal congestion/runny nose, body pains (myalgia), fatigue (malaise), diarrhoea, abdominal pain, anorexia, nausea or vomiting without evidence of pneumonia or hypoxia
* Moderate pneumonia -Clinical signs of pneumonia (fever, cough, dyspnoea, fast breathing) with no need for supplemental oxygen (oxygen saturation ≥90%% on room air or RR between 20 and 30bpm).

Household contacts - Individuals ≥ 5 years of age living in the same household with the index cases from cohort 1 will be offered to participate into the study. Living in the same household is defined as those individuals who are planning to sleep in and eat from same 'cooking pot' during the following 2 weeks.

Cohort 2:

Individuals ≥12 years of age with suspected or confirmed COVID-19 associated severe pneumonia defined as signs of pneumonia (fever, cough, dyspnoea or fast breathing) plus one of: oxygen saturation (SpO2) \<90% on room air OR respiratory rate \> 30 breaths/minute

Suspected COVID-19 disease is defined as clinically or radiologically suspected as determined by the most senior clinician available:

1. Clinically suspected Signs and symptoms of pneumonia (as defined above) AND patient living in or recent travel to region with community transmission OR close contact with known COVID-19 patient AND no alternative diagnosis to explain the clinical picture OR
2. Radiologically suspected Typical radiological signs of COVID-19 on chest X-ray or lung ultrasound

Exclusion Criteria:

* Pregnant women will be excluded from both Cohort 1 and Cohort 2. Patients with allergies to the investigational products will be excluded Cohort 1 (Ivermectin) Lactating mothers will be excluded

Cohort 2 (aspirin):

* Taking aspirin or other non steroidal anti-inflammatory drugs for any reason.
* Any bleeding disorder (e.g. frequent nose bleeds, haemophilia)
* Active or recurrent peptic ulcer disease (defined as currently on triple therapy or had more than 1 course of triple therapy in the past 12 months. Do not count symptoms of gastritis or on omeprazole as peptic ulcer disease)
* Current active gastrointestinal haemorrhage
* Severe liver disease or severe kidney disease (severe liver disease defined as cirrhosis with portal hypertension and history of variceal bleeding; severe kidney disease defined as stage 4/5 KD, eGFR \<30ml/min)
* Gout
* Suspected intra-cerebral haemorrhage
* Diagnosed with a stroke on this admission

Primary outcomes:
measure: Cohort 1 Index Case: Percentage of patients with COVID-19 associated mild disease/moderate pneumonia progressing to severe pneumonia [Time frame 14 days]
timeFrame: 14 days
measure: Cohort 1 Household contacts: Percentage of HH members that get infected with SARS-CoV-2 [Time frame 14 days]
timeFrame: 14 days
measure: Cohort 2: Percentage of COVID-19 associated severe pneumonia patients worsening their condition [Time frame at discharge or day 28 (whichever is first)]
timeFrame: up to 28 days
Secondary outcomes:
measure: Cohort1 Index cases: Days from recruitment to virological clearance [Time frame 28 days]
timeFrame: 28 days
measure: Days from recruitment until clinical recovery
timeFrame: 28 days
measure: - IgG geometric mean titre (GMT) at day 14 and 28 after recruitment [Time frame 14 days and 28 days]
timeFrame: 14 days and 28 days
measure: Household contacts IgG geometric mean titre (GMT) at day 14 after recruitment [Time frame 14 days]
timeFrame: 14 days
measure: Percentage of HH members infected that develop COVID19 symptoms [Time frame 14 days]
timeFrame: 14 days
measure: Cohort 2 - Hours from recruitment to hospital discharge [Time frame at discharge]
timeFrame: up to 28 days
measure: - Hours of duration on oxygen supplementation [Time frame at discharge or day 28 (whichever is first)]
timeFrame: at discharge or day 28 (whichever is first)
measure: - Death ratio during hospitalization [Time frame at time of death]
timeFrame: up to 28 days
measure: - Death ratio at 28 days after enrolment [Time frame 28 days]
timeFrame: 28 days
measure: - Death ratio at 90 days after enrolment [Time frame 90 days]
timeFrame: 90 days
measure: - Occurrence of clinical thrombotic and embolic events (myocardial infarction, pulmonary embolus, deep venous thrombosis, cerebrovascular accidents). [Time frame 90 days]
timeFrame: 90 days
measure: - Occurrence of clinical episodes of gastrointestinal bleeding [Time frame 90 days]
timeFrame: 90 days
measure: - Change in CRP and D-Dimer levels between baseline (enrolment) and day 3-5 [Time frame 5 days]
timeFrame: enrolment / days 3-5
measure: - Persisting breathlessness at 28 days and 90 days after enrolment [Time frame 28 days/90 days ]
timeFrame: at 28 day and at 90 day
measure: - Self-reported health at 28 days and 90 days [Time frame 28 days/ 90 days]
timeFrame: at 28 days and 90 days
Other outcomes:
Locations:
city: Fajara
country: Gambia
facility: Mrcg@Lshtm
Study officials:
affiliation: Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine
name: Effua Usuf, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine
name: Behzad Nadjm, MBChB, FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine
name: Anna Roca, PhD
role: STUDY_DIRECTOR
References:
citation: Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.