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

NCT04703608 | Unknown Phase 3 DMC

• 1 other identifier: LEO 22628
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid-19

Outcome Measures

Primary Outcomes (3)

• Cohort 1 Index Case: Percentage of patients with COVID-19 associated mild disease/moderate pneumonia progressing to severe pneumonia [Time frame 14 days]

  Percentage of patients with COVID-19 associated mild disease/moderate pneumonia progressing within 14 days after recruitment into severe pneumonia (as per WHO definitions of severity, for each age group)

  14 days

• Cohort 1 Household contacts: Percentage of HH members that get infected with SARS-CoV-2 [Time frame 14 days]

  Percentage of HH members that get infected with SARS-CoV-2 during the 14 days following recruitment (defined as those RT-PCR and IgM/IgG negative at day 1 who become positive either by RT-PCR or IgM/IgG by day 14)

  14 days

• Cohort 2: Percentage of COVID-19 associated severe pneumonia patients worsening their condition [Time frame at discharge or day 28 (whichever is first)]

  Percentage of COVID-19 associated severe pneumonia patients meeting the criteria of failure defined as worsening their condition from baseline (on admission) for a period of at least 24 hours, scale as follows: * On or requiring supplemental oxygen given by nasal cannula or face mask to maintain SpO2 within target range * On or requiring non-invasive (eg CPAP or BiPAP) or invasive ventilatory support to maintain SpO2 within target range (or not maintaining SpO2 within target range with supplemental oxygen given by nasal cannula or face mask) * Death during hospitalization

  up to 28 days

Secondary Outcomes (15)

• Cohort1 Index cases: Days from recruitment to virological clearance [Time frame 28 days]

  28 days

• Days from recruitment until clinical recovery

  28 days

• - IgG geometric mean titre (GMT) at day 14 and 28 after recruitment [Time frame 14 days and 28 days]

  14 days and 28 days

• Household contacts IgG geometric mean titre (GMT) at day 14 after recruitment [Time frame 14 days]

  14 days

• Percentage of HH members infected that develop COVID19 symptoms [Time frame 14 days]

  14 days

Study Arms (5)

Arm 1 of Cohort 1

EXPERIMENTAL

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

Drug: Ivermectin

Arm 2 of Cohort 1

EXPERIMENTAL

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

Drug: Ivermectin; Drug: Placebo

Arm 3 of Cohort 1

PLACEBO COMPARATOR

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

Drug: Placebo

Arm 1 of Cohort 2

EXPERIMENTAL

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

Drug: ASP

Arm 2 of Cohort 2

PLACEBO COMPARATOR

Non identical placebo; doses as per above

Drug: Placebo

Interventions

Ivermectin DRUG

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

Arm 1 of Cohort 1; Arm 2 of Cohort 1

ASP DRUG

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

Arm 1 of Cohort 2

Placebo DRUG

Non-identical placebo

Arm 2 of Cohort 1; Arm 2 of Cohort 2; Arm 3 of Cohort 1

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• Radiologically suspected Typical radiological signs of COVID-19 on chest X-ray or lung ultrasound

You may not qualify if:

• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead

Study Sites (1)

Mrcg@Lshtm

Fajara, The Gambia

RECRUITING

Related Publications (2)

• 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.

  PMID: 37489818 DERIVED

• 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.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Ivermectin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Effua Usuf, MBChB, PhD

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

  PRINCIPAL INVESTIGATOR

• Behzad Nadjm, MBChB, FRCP

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

  PRINCIPAL INVESTIGATOR

• Anna Roca, PhD

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

  STUDY DIRECTOR

Central Study Contacts

Anna Roca, PhD

CONTACT

+220 4495442; aroca@mrc.gm

Effua Usuf, MBChB, PhD

CONTACT

+220 4495442; eusuf@mrc.gm

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single blind non-identical placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two cohorts study as follows: * Cohort 1: intervention with Ivermectin * Cohort 2: intervention with Aspirin Parallel assignment

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 11, 2021
• Study Start: January 22, 2021
• Primary Completion: March 1, 2022
• Study Completion: July 1, 2022
• Last Updated: June 4, 2021

Record last verified: 2021-06

Locations

TH (1)