Clinical trial NCT04672590: COVID-19 Neurological Disease: A Prospective Study
Official title: COVID-19 Neurological Disease: A Prospective Study in Brazil, India and Malawi
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diseases of the Nervous System
Other Specified Viral Diseases
Lead sponsor: University of Liverpool
Sponsor class: OTHER
Collaborators: name: Christian Medical College, Vellore, India
name: Instituto Autoimune, Brazil
name: University College London Hospitals
name: Oswaldo Cruz Foundation
name: Kamuzu University of Health Sciences
name: National Institute of Mental Health and Neuro Sciences, India
name: Encephalitis Society, UK
First posted: 2020-12-17
Enrollment: 1017
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cases: Hospitalised patients with acute new-onset neurological disease and COVID-19

Controls: Hospitalised patients with COVID-19, without acute new-onset neurological disease

Brief summary: Background: Recent reports increasingly recognize neurological manifestations in COVID-19 patients. However, the full spectrum of the disease and risk factors are not well understood.

Aim: To describe the full spectrum of neurological manifestations in COVID-19 and assess the clinical characteristics, risks and prognostic factors.

Outcomes: Identification of COVID-19 associated neurological disease is the primary outcome while requirement for admission to critical care unit, mortality, length of hospital stay, quality of life, and neurological disability are the secondary outcomes.

Participants: Patients above Age more than 18 years enrolled based on new-onset acute neurological disease and COVID19 positive will serve as cases while patient with confirmed COVID-19 without neurological manifestation will serve as controls.

Design and Procedures: The study is prospective case control in design and is divided into three phases in India, Brazil and Malawi ; the first phase will address role of hypoxia in causation of neurological diseases, the second phase will compare characteristics of patients hospitalized with COVID-19 with and without neurological disease and the third phase will assess the long-term follow up (at 3 months and 9 months) of cases.


Eligibility criteria: Cases

Inclusion criteria:

1. Confirmed or probable new-onset acute neurological disease (according to study definitions) AND
2. Confirmed or probable COVID-19 (according to study definitions), diagnosed using tests performed no later than 5 days after presentation with neurological disease

Exclusion criteria (any of):

* Age \<18 years
* Neurological features are explained fully by a previous neurological disease
* PCR test performed \>5 days after admission to hospital, in the absence of clinical illness meeting criteria for suspected COVID-19 (to exclude those with hospital-acquired infection).
* Enrolled on the basis of new-onset acute neurological disease, but subsequently does not meet definition for probable or confirmed COVID-19.

Controls

Two controls with non-neurological COVID-19 will be recruited per case.

They will meet all of the following criteria:

* Adults, no more than 5 years younger or older than the case.
* Enrolled at a similar time since admission to hospital as the case, defined as: \<7 days; 7-13 days inclusive; or ≥14 days.
* Hospitalised patients with confirmed or probable COVID-19 (according to study definitions)
* Not meeting criteria for confirmed or probable new-onset acute neurological disease (according to study definitions).

Some potential controls may be reclassified as cases if they develop neurological manifestations at up to 30 days after admission to hospital.

Primary outcomes:
measure: Acute new-onset neurological disease
timeFrame: Day 30 of admission, or at discharge, or at death, whichever is earlier
Secondary outcomes:
measure: Admission to a critical (intensive/high dependency) care unit
timeFrame: Day 30 of admission, or at discharge, or at death, whichever is earlier
measure: Time to discharge from hospital
timeFrame: Day 30 of admission, or at discharge, or at death, whichever is earlier
measure: Severity of stroke using National Institutes of Health Stroke Scale (NIHSS)
timeFrame: Day 30 of admission, or at discharge, or at death, whichever is earlier
measure: Glasgow Outcome Scale Extended
timeFrame: Discharge (or day 30), 3 months and 9 months
measure: Modified Rankin Score
timeFrame: Discharge (or day 30), 3 months and 9 months
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Discharge (or day 30), 3 months and 9 months
measure: Development of new onset neurological sequelae
timeFrame: Discharge (or day 30), 3 months and 9 months
measure: European QoL-5D (EQ-5D-3L) overall health utility quality of life score
timeFrame: Discharge (or day 30), 3 months and 9 months
measure: Death
timeFrame: In-hospital (up to 30 days from admission), and at 3 months and 9 months
Other outcomes:
Locations:
city: Recife
country: Brazil
facility: FioCruz
city: Bangalore
country: India
facility: National Institute of Mental Health and Neurosciences
city: Vellore
country: India
facility: Christian Medical College
city: Blantyre
country: Malawi
facility: Malawi Liverpool Wellcome Clinical Research Programme
city: Blantyre
country: Malawi
facility: Kamuzu University of Health Sciences
Study officials:
affiliation: University of Liverpool
name: Tom Solomon, PhD
role: PRINCIPAL_INVESTIGATOR
References: