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

NCT ID: NCT04703608

Last Updated: 2021-06-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 1200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-22
• Study Completion Date: 2022-07-31

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).

Conditions

Covid-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Arm 1 of Cohort 1

Index Case / Household members Ivermectin / Ivermectin (with preventative package)

Group Type: EXPERIMENTAL

Ivermectin

Intervention Type: DRUG

Ivermectin 0.3-0.4mg/Kg daily for 3 days.

Arm 2 of Cohort 1

Index Case / Household members Ivermectin / Placebo (with preventative package)

Group Type: EXPERIMENTAL

Ivermectin

Intervention Type: DRUG

Ivermectin 0.3-0.4mg/Kg daily for 3 days.

Placebo

Intervention Type: DRUG

Non-identical placebo

Arm 3 of Cohort 1

Index Case / Household members Placebo / Placebo (with preventative package)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Non-identical placebo

Arm 1 of Cohort 2

Aspirin 150mg daily for 28 days or until hospital discharge or death (whichever is sooner)

Group Type: EXPERIMENTAL

ASP

Intervention Type: DRUG

Aspirin 150mg daily for 28 days or until hospital discharge (whichever is sooner)

Arm 2 of Cohort 2

Non identical placebo; doses as per above

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Non-identical placebo

Interventions

Ivermectin

Ivermectin 0.3-0.4mg/Kg daily for 3 days.

Intervention Type: DRUG

ASP

Aspirin 150mg daily for 28 days or until hospital discharge (whichever is sooner)

Intervention Type: DRUG

Placebo

Non-identical placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Effua Usuf, MBChB, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine

Behzad Nadjm, MBChB, FRCP

Role: PRINCIPAL_INVESTIGATOR

Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine

Anna Roca, PhD

Role: STUDY_DIRECTOR

Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine

Locations

Mrcg@Lshtm

Fajara, , The Gambia

Site Status: RECRUITING

Countries

The Gambia

Central Contacts

Anna Roca, PhD

Role: CONTACT

aroca@mrc.gm

+220 4495442 ext. 2305

Effua Usuf, MBChB, PhD

Role: CONTACT

eusuf@mrc.gm

+220 4495442 ext. 5014

Facility Contacts

Effua Usuf, MBChB

Role: primary

eusuf@mrc.gm

+2204495442-6 ext. 5014

Behzad Nadjm, MBChB

Role: backup

bnadjm@mrc.gm

+2204495442-6 ext. 2123

References

Fischer AL, Messer S, Riera R, Martimbianco ALC, Stegemann M, Estcourt LJ, Weibel S, Monsef I, Andreas M, Pacheco RL, Skoetz N. Antiplatelet agents for the treatment of adults with COVID-19. Cochrane Database Syst Rev. 2023 Jul 25;7(7):CD015078. doi: 10.1002/14651858.CD015078.

Reference Type: DERIVED

PMID: 37489818 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

Other Identifiers

LEO 22628

Identifier Type: -

Identifier Source: org_study_id