Statin TReatment for COVID-19 to Optimise NeuroloGical recovERy

NCT04904536 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: X21-0113
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Neurocognitive Impairment, Mild

Keywords

clinical trial; COVID-19; neurological symptoms; atorvastatin

Outcome Measures

Primary Outcomes (1)

• Neurological Recovery

  Processing speed, assessed on the oral Symbol Digit Modalities Test (SDMT)

  12 months

Secondary Outcomes (1)

• Brain Imaging

  12 months

Study Arms (2)

Study Medication Arm

EXPERIMENTAL

6-monthly supplies of atorvastatin 40mg on top of standard care for a period of 12 months.

Drug: Atorvastatin

Standard Care Arm

ACTIVE COMPARATOR

Standard care for a period of 12 months.

Other: Standard Care

Interventions

Atorvastatin DRUG

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.

Study Medication Arm

Standard Care OTHER

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

Standard Care Arm

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The George Institute: lead
• University of Sydney: collaborator
• Monash University: collaborator
• The Alfred: collaborator
• Universidad del Desarrollo: collaborator
• Chinese University of Hong Kong: collaborator
• Clinica Alemana de Santiago: collaborator

Study Sites (1)

The George Institute for Global Health

Sydney, New South Wales, 2050, Australia

Location

Related Publications (1)

• Delfino C, Carcel C, Lin X, Munoz-Venturelli P, Naismith SL, Woodward M, Peters R, Wijesuriya N, Law M, Harding IH, Wang X, Elliott J, Leder K, Hutchings O, Stecher X, Zoungas S, Anderson CS. STatin TReatment for COVID-19 to Optimise NeuroloGical recovERy (STRONGER): study protocol for a randomised, open label clinical trial in patients with persistent neurological symptoms after COVID-19 infection. BMJ Open. 2025 Apr 14;15(4):e089382. doi: 10.1136/bmjopen-2024-089382.

  PMID: 40228860 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular; COVID-19; Neurologic Manifestations

Interventions

Atorvastatin; Standard of Care

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Craig Anderson, MD

  The George Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2021
• First Posted: May 27, 2021
• Study Start: March 10, 2022
• Primary Completion: June 30, 2025
• Study Completion: July 30, 2025
• Last Updated: April 10, 2025

Record last verified: 2025-04

Locations

AU (1)