Prevention and Treatment for COVID -19 (Severe Acute Respiratory Syndrome Coronavirus 2 SARS-CoV-2) Associated Severe Pneumonia in the Gambia
Prevention and Treatment for COVID -19 (Severe Acute Respiratory Syndrome Coronavirus 2 SARS-CoV-2) Associated Severe Pneumonia in the Gambia
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.
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).
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