Statin TReatment for COVID-19 to Optimise NeuroloGical recovERy (STRONGER)

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

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 12 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neurocognitive Impairment, Mild
• Intervention / Treatment: Other: Standard Care; Drug: Atorvastatin

Detailed Description

Question: Does treatment with 40mg atorvastatin over 12 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 are established at centralised research clinics located at: The Brain and Mind Centre of the University of Sydney; Alfred Medical Centre linked to Monash University, a research clinic associated with Clínica Alemana Universidad del Desarrollo, Santiago, Chile, and a research clinic associated with The Chinese University of Hong Kong. Additional sites may be set up as required.

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • The George Institute for Global Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• History of COVID-19 that is confirmed by a positive polymerase-chain-reaction (PCR) test,rapid antigen test (RAT) or as per the state guidelines for COVID-19 diagnosis at the time of screening
• 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 in conjunction with clinical assessment)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Medication Arm; 6-monthly supplies of atorvastatin 40mg on top of standard care for a period of 12 months.	Drug: Atorvastatin; 40mg atorvastatin + standard care daily for 12 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. Similarly, a comparable atorvastatin 40mg is being sourced in Hong Kong, and will be dispensed from the site's pharmacy.
Active Comparator: Standard Care Arm; Standard care for a period of 12 months.	Other: Standard Care; Standard care for neurological symptoms as a result of COVID-19 infection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological Recovery	Processing speed, assessed on the oral Symbol Digit Modalities Test (SDMT)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Imaging	White matter free water measured on diffusion MRI brain imaging	12 months

Collaborators and Investigators

• Sponsor: The George Institute
• Collaborators: Chinese University of Hong Kong; Monash University; The Alfred; University of Sydney; Universidad del Desarrollo; Clinica Alemana de Santiago
• Investigators: Principal Investigator: Craig Anderson, MD, The George Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: COVID-19; clinical trial; atorvastatin; neurological symptoms
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: X21-0113

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No