STRONGER: Statin TReatment for COVID-19 to Optimise NeuroloGical recovERy

Sponsor

The George Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04904536

Collaborator

University of Sydney (Other), Monash University (Other), The Alfred (Other), Universidad del Desarrollo (Other)

400

Enrollment

Location

Arms

14.7

Anticipated Duration (Months)

27.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

STRONGER is an international, investigator initiated and conducted, pragmatic clinical trial to determine whether 40mg atorvastatin daily can improve neurocognitive function in adults with long COVID neurological symptoms. The objective is to determine effectiveness of treatment with 40mg atorvastatin over 18 months on attenuating cognitive decline and neuroinflammatory biomarkers in adults with long COVID neurological symptoms. The study design is a prospective, randomised, open-label, blinded endpoint (PROBE) study of atorvastatin 40mg on top of standard care, in patients with long COVID neurological symptoms.

Condition or Disease	Intervention/Treatment	Phase
Neurocognitive Impairment, Mild	Drug: Atorvastatin Other: Standard Care	Phase 3

Detailed Description

Question: Does treatment with 40mg atorvastatin over 18 months attenuate cognitive decline and neuroinflammatory biomarkers in adults with long COVID neurological symptoms? Aims: In 410 adults who report ongoing alteration of their memory, thinking, concentration or mood after COVID-19 diagnosis, this pragmatic clinical trial aims to determine the effects of standard-dose atorvastatin on improving neurological outcomes with sensitive measures of cognitive function and brain MRI.

Outcome measures include; Primary - processing speed, assessed on the oral Symbol Digit Modalities Test (SDMT). Key Secondary - white matter free water measured on diffusion MRI brain imaging. Other - other components of cognitive function; other health assessments; other MRI markers of cerebral white matter integrity, iron load, cerebral perfusion, and glutathione for oxidative stress; cost-effectiveness compared to standard care. The study sites will be established at centralised research clinics located at: The Brain and Mind Centre of the University of Sydney; Alfred Medical Centre linked to Monash University, and a research clinic associated with Clínica Alemana Universidad del Desarrollo, Santiago, Chile. Additional sites may be set up as required.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

An International, Investigator Initiated and Conducted, Pragmatic Clinical Trial to Determine Whether 40mg Atorvastatin Daily Can Improve Neurocognitive Function in Adults With Long COVID Neurological Symptoms

Actual Study Start Date :

Mar 10, 2022

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study Medication Arm 6-monthly supplies of atorvastatin 40mg on top of standard care for a period of 18 months.	Drug: Atorvastatin 40mg atorvastatin + standard care daily for 18 months.Atorvastatin 40mg has TGA approval for general marketing for the treatment of hypercholesterolaemia and cardiovascular prevention under a number of manufacturer names.The study medication selected will be the atorvastatin 40mg (Apotex) which is scored, and allows down-titration to 20mg should a participant develop symptoms.The study medication will be packaged, labelled and dispensed directly to particpants by the Syntro Health pharmacy in Australia. A comparable atorvastatin 40mg is being sourced in Chile, and will be dispensed from the pharmacy of the Clínica Alemana de Santiago.
Active Comparator: Standard Care Arm Standard care for a period of 18 months.	Other: Standard Care Standard care for neurological symptoms as a result of COVID-19 infection.

Arm

Intervention/Treatment

Experimental: Study Medication Arm

6-monthly supplies of atorvastatin 40mg on top of standard care for a period of 18 months.

Drug: Atorvastatin

40mg atorvastatin + standard care daily for 18 months.Atorvastatin 40mg has TGA approval for general marketing for the treatment of hypercholesterolaemia and cardiovascular prevention under a number of manufacturer names.The study medication selected will be the atorvastatin 40mg (Apotex) which is scored, and allows down-titration to 20mg should a participant develop symptoms.The study medication will be packaged, labelled and dispensed directly to particpants by the Syntro Health pharmacy in Australia. A comparable atorvastatin 40mg is being sourced in Chile, and will be dispensed from the pharmacy of the Clínica Alemana de Santiago.

Active Comparator: Standard Care Arm

Standard care for a period of 18 months.

Other: Standard Care

Standard care for neurological symptoms as a result of COVID-19 infection.

Outcome Measures

Primary Outcome Measures

Neurological Recovery [18 months]
Processing speed, assessed on the oral Symbol Digit Modalities Test (SDMT)

Secondary Outcome Measures

Brain Imaging [18 months]
White matter free water measured on diffusion MRI brain imaging

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years
History of COVID-19 that is confirmed by a positive polymerase-chain-reaction (PCR) test
Any ongoing neurological symptoms as a result of COVID-19 (e.g. problems with memory, concentration, sleep disturbance and fatigue) that are identified through administration of the checklist of symptoms on the Somatic and Psychological Health Report (SPHERE) questionnaire, or reported loss of smell (anosmia)
Able to fully participate in all procedures, including cognitive assessments
Able and willing to provide written informed consent

Exclusion Criteria:

Evidence of dementia and/or significant cognitive impairment on screening (i.e. Blind Montreal Cognitive Assessment [MoCA] score <19/22)
Severe co-morbid medical or psychiatric condition that prevents participation
History of traumatic brain injury with loss of consciousness (>30 mins) within the last 2 years
Ongoing long-term use for a clear indication (e.g. secondary cardiovascular prevention in high-risk individuals) or any contraindication (e.g. previous adverse reaction) of statin use
Evidence of severe or significant liver disease, defined as any of the following: acute viral hepatitis; chronic active hepatitis; chronic active hepatitis; cirrhosis; or elevated biochemical function markers i.e. ALT or AST >3x the ULN or eGFR <30mL/min/1.73m2
Creatine kinase (CK) levels > 2x upper limit of normal (ULN)
Female of child-bearing potential that is unable or unwilling to use reliable method of contraception, breastfeeding, or planning a pregnancy
For a sub-group of participants undergoing MRI - any contraindication to MRI due to metallic body parts or claustrophobia
Medical history of a disorder that might, in the opinion of the attending clinician, put the participant at significant risk if they were to participate in the trial