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).
Drug: Ivermectin
Ivermectin 0.3-0.4mg/Kg daily for 3 days.
Drug: ASP
Aspirin 150mg daily for 28 days or until hospital discharge (whichever is sooner)
Drug: Placebo
Non-identical placebo
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
Mrcg@Lshtm
Fajara, Gambia
Investigator: Effua Usuf, MBChB
Contact: +2204495442-6
eusuf@mrc.gm
Anna Roca, PhD
+220 4495442 - 2305
aroca@mrc.gm
Effua Usuf, MBChB, PhD
+220 4495442 - 5014
eusuf@mrc.gm