Back to resultsPrevention and Treatment for COVID -19 (Severe Acute Respiratory Syndrome Coronavirus 2 SARS-CoV-2) Associated Severe Pneumonia in the Gambia (PaTS-COVID)
Primary Purpose
Covid-19
Status
Unknown status
Phase
Phase 3
Locations
Gambia
Study Type
Interventional
Intervention
Ivermectin
ASP
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Covid-19
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:
- 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
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
Sites / Locations
- Mrcg@LshtmRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Arm 1 of Cohort 1
Arm 2 of Cohort 1
Arm 3 of Cohort 1
Arm 1 of Cohort 2
Arm 2 of Cohort 2
Arm Description
Index Case / Household members Ivermectin / Ivermectin (with preventative package)
Index Case / Household members Ivermectin / Placebo (with preventative package)
Index Case / Household members Placebo / Placebo (with preventative package)
Aspirin 150mg daily for 28 days or until hospital discharge or death (whichever is sooner)
Non identical placebo; doses as per above
Outcomes
Primary Outcome Measures
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)
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)
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
Secondary Outcome Measures
Cohort1 Index cases: Days from recruitment to virological clearance [Time frame 28 days]
- Days from recruitment to virological clearance defined as one negative SARS-CoV2 virus RT-PCRs.
Days from recruitment until clinical recovery
- Days from recruitment until clinical recovery defined as two consecutive days of no fever (T ≤37.50C) and normal respiratory rate (as per normal range for age and WHO definitions) (only once if day 28 as end of follow-up
- IgG geometric mean titre (GMT) at day 14 and 28 after recruitment [Time frame 14 days and 28 days]
Household contacts IgG geometric mean titre (GMT) at day 14 after recruitment [Time frame 14 days]
Percentage of HH members infected that develop COVID19 symptoms [Time frame 14 days]
(defined as those asymptomatic at day 1 that become symptomatic by day 14 (COVID-19 positive either by RT-PCR or IgM/IgG and meet criteria for Cohort 1 index case or cohort 2)
Cohort 2 - Hours from recruitment to hospital discharge [Time frame at discharge]
- Hours of duration on oxygen supplementation [Time frame at discharge or day 28 (whichever is first)]
- Death ratio during hospitalization [Time frame at time of death]
- Death ratio at 28 days after enrolment [Time frame 28 days]
- Death ratio at 90 days after enrolment [Time frame 90 days]
- Occurrence of clinical thrombotic and embolic events (myocardial infarction, pulmonary embolus, deep venous thrombosis, cerebrovascular accidents). [Time frame 90 days]
- Occurrence of clinical episodes of gastrointestinal bleeding [Time frame 90 days]
- Change in CRP and D-Dimer levels between baseline (enrolment) and day 3-5 [Time frame 5 days]
- Persisting breathlessness at 28 days and 90 days after enrolment [Time frame 28 days/90 days ]
- Self-reported health at 28 days and 90 days [Time frame 28 days/ 90 days]
Poor self-reported health assessed by a linear self-reported health scale from the EQ-5D questionnaire in person or by telephone
Full Information
NCT ID
NCT04703608
First Posted
January 6, 2021
Last Updated
June 3, 2021
Sponsor
London School of Hygiene and Tropical Medicine
1. Study Identification
Unique Protocol Identification Number
NCT04703608
Brief Title
Prevention and Treatment for COVID -19 (Severe Acute Respiratory Syndrome Coronavirus 2 SARS-CoV-2) Associated Severe Pneumonia in the Gambia
Acronym
PaTS-COVID
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
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 22, 2021 (Actual)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
July 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
London School of Hygiene and Tropical Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Two cohorts study as follows:
Cohort 1: intervention with Ivermectin
Cohort 2: intervention with Aspirin Parallel assignment
Masking
Participant
Masking Description
Single blind non-identical placebo
Allocation
Randomized
Enrollment
1200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 of Cohort 1
Arm Type
Experimental
Arm Description
Index Case / Household members Ivermectin / Ivermectin (with preventative package)
Arm Title
Arm 2 of Cohort 1
Arm Type
Experimental
Arm Description
Index Case / Household members Ivermectin / Placebo (with preventative package)
Arm Title
Arm 3 of Cohort 1
Arm Type
Placebo Comparator
Arm Description
Index Case / Household members Placebo / Placebo (with preventative package)
Arm Title
Arm 1 of Cohort 2
Arm Type
Experimental
Arm Description
Aspirin 150mg daily for 28 days or until hospital discharge or death (whichever is sooner)
Arm Title
Arm 2 of Cohort 2
Arm Type
Placebo Comparator
Arm Description
Non identical placebo; doses as per above
Intervention Type
Drug
Intervention Name(s)
Ivermectin
Intervention Description
Ivermectin 0.3-0.4mg/Kg daily for 3 days.
Intervention Type
Drug
Intervention Name(s)
ASP
Intervention Description
Aspirin 150mg daily for 28 days or until hospital discharge (whichever is sooner)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Non-identical placebo
Primary Outcome Measure Information:
Title
Cohort 1 Index Case: Percentage of patients with COVID-19 associated mild disease/moderate pneumonia progressing to severe pneumonia [Time frame 14 days]
Description
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)
Time Frame
14 days
Title
Cohort 1 Household contacts: Percentage of HH members that get infected with SARS-CoV-2 [Time frame 14 days]
Description
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)
Time Frame
14 days
Title
Cohort 2: Percentage of COVID-19 associated severe pneumonia patients worsening their condition [Time frame at discharge or day 28 (whichever is first)]
Description
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
Time Frame
up to 28 days
Secondary Outcome Measure Information:
Title
Cohort1 Index cases: Days from recruitment to virological clearance [Time frame 28 days]
Description
- Days from recruitment to virological clearance defined as one negative SARS-CoV2 virus RT-PCRs.
Time Frame
28 days
Title
Days from recruitment until clinical recovery
Description
- Days from recruitment until clinical recovery defined as two consecutive days of no fever (T ≤37.50C) and normal respiratory rate (as per normal range for age and WHO definitions) (only once if day 28 as end of follow-up
Time Frame
28 days
Title
- IgG geometric mean titre (GMT) at day 14 and 28 after recruitment [Time frame 14 days and 28 days]
Time Frame
14 days and 28 days
Title
Household contacts IgG geometric mean titre (GMT) at day 14 after recruitment [Time frame 14 days]
Time Frame
14 days
Title
Percentage of HH members infected that develop COVID19 symptoms [Time frame 14 days]
Description
(defined as those asymptomatic at day 1 that become symptomatic by day 14 (COVID-19 positive either by RT-PCR or IgM/IgG and meet criteria for Cohort 1 index case or cohort 2)
Time Frame
14 days
Title
Cohort 2 - Hours from recruitment to hospital discharge [Time frame at discharge]
Time Frame
up to 28 days
Title
- Hours of duration on oxygen supplementation [Time frame at discharge or day 28 (whichever is first)]
Time Frame
at discharge or day 28 (whichever is first)
Title
- Death ratio during hospitalization [Time frame at time of death]
Time Frame
up to 28 days
Title
- Death ratio at 28 days after enrolment [Time frame 28 days]
Time Frame
28 days
Title
- Death ratio at 90 days after enrolment [Time frame 90 days]
Time Frame
90 days
Title
- Occurrence of clinical thrombotic and embolic events (myocardial infarction, pulmonary embolus, deep venous thrombosis, cerebrovascular accidents). [Time frame 90 days]
Time Frame
90 days
Title
- Occurrence of clinical episodes of gastrointestinal bleeding [Time frame 90 days]
Time Frame
90 days
Title
- Change in CRP and D-Dimer levels between baseline (enrolment) and day 3-5 [Time frame 5 days]
Time Frame
enrolment / days 3-5
Title
- Persisting breathlessness at 28 days and 90 days after enrolment [Time frame 28 days/90 days ]
Time Frame
at 28 day and at 90 day
Title
- Self-reported health at 28 days and 90 days [Time frame 28 days/ 90 days]
Description
Poor self-reported health assessed by a linear self-reported health scale from the EQ-5D questionnaire in person or by telephone
Time Frame
at 28 days and 90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
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:
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Roca, PhD
Phone
+220 4495442
Ext
2305
Email
aroca@mrc.gm
First Name & Middle Initial & Last Name or Official Title & Degree
Effua Usuf, MBChB, PhD
Phone
+220 4495442
Ext
5014
Email
eusuf@mrc.gm
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Effua Usuf, MBChB, PhD
Organizational Affiliation
Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Behzad Nadjm, MBChB, FRCP
Organizational Affiliation
Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anna Roca, PhD
Organizational Affiliation
Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine
Official's Role
Study Director
Facility Information:
Facility Name
Mrcg@Lshtm
City
Fajara
Country
Gambia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Effua Usuf, MBChB
Phone
+2204495442-6
Ext
5014
Email
eusuf@mrc.gm
First Name & Middle Initial & Last Name & Degree
Behzad Nadjm, MBChB
Phone
+2204495442-6
Ext
2123
Email
bnadjm@mrc.gm
12. IPD Sharing Statement
Citations:
PubMed Identifier
34473343
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.
Results Reference
derived
Learn more about this trial
Prevention and Treatment for COVID -19 (Severe Acute Respiratory Syndrome Coronavirus 2 SARS-CoV-2) Associated Severe Pneumonia in the Gambia
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