STREAM Trial - Biomarker

NCT05482386 | Recruiting DMC

• 3 other identifiers: STREAM-Biomarker32003B_205067FF21106
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Statins are among the most widely used drugs. While they were found to be effective for primary and secondary prevention of cardiovascular disease (CVD) in middle-aged subjects, their benefits for primary prevention in older adults (aged ≥70 years) without CVD are uncertain, particularly for those with multimorbidity. Older patients with elevated biomarkers associated with cardiovascular (CV) risk might benefit from continuing statins to prevent CV outcomes, but this hypothesis has not been rigorously tested in randomized clinical trials (RCTs). To address these questions, the investigators conduct a RCT in 500 multimorbid adults ≥70 years old taking statins for primary prevention who will be randomized to statin continuation vs. statin discontinuation, and measure baseline biomarkers to determine if the risk of a composite outcome of CV events and all-cause mortality after statin discontinuation differs among those with baseline levels of previously validated blood biomarkers associated with increased risk of CV outcomes.

Conditions

Statin Treatment for Primary Prevention

Keywords

Cardiovascular biomarkers; Statins; Primary prevention; Multimorbidity; Older adults

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke)

  The primary endpoint is a composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke). All-cause death (and not CV death only) is chosen to account for a possible shift from CV to other causes of death. The composite endpoint was selected to assess the net clinical benefit in this population with expected high mortality. The clinical event committee which classifies suspected events for the primary and secondary clinical outcomes is blinded.

  Up to 48 months

Secondary Outcomes (10)

• All-cause death

  Up to 48 months

• Non-CV death

  Up to 48 months

• Major CV events

  Up to 48 months

• Total CV events

  Up to 48 months

• Total composite events

  Up to 48 months

Study Arms (2)

Statin discontinuation

EXPERIMENTAL

Discontinuation of statin therapy - statin therapy will be stopped from the next scheduled intake after study inclusion (intervention arm).

Other: Statin discontinuation

Statin continuation

NO INTERVENTION

Continuation of statin therapy - no change in the prescribed statin therapy (control arm).

Interventions

Statin discontinuation OTHER

Statin therapy will be stopped. Additional lipid-lowering medication lowering LDL cholesterol will also be stopped.

Also known as: Intervention arm

Statin discontinuation

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• ≥70 years of age
• Multimorbid with ≥2 coexistent chronic conditions (defined by ICD-10 codes) with an estimated duration of 6 months or more based on clinical decision, besides dyslipidemia treated by statins
• Taking a statin for ≥80% of the time during the year before baseline

You may not qualify if:

• Secondary prevention based on previous large statin trials, defined as:
• History of myocardial infarction type 12 (NSTEMI/STEMI) OR
• History of unstable angina, defined as ACS symptomatic at rest, crescendo or new-onset angina (CCS 2 or 3) without ECG or cardiac biomarker changes (based on available documents) OR
• Stable angina pectoris with a documented ischemia on a stress test or with a significant coronary disease defined as a coronary stenosis \>50% OR
• History of percutaneous coronary intervention (balloon or stent) or coronary artery bypass graft OR
• History of ischemic stroke OR
• History of Transient Ischemic Attack, defined as transient neurological deficit without diffusion restriction in MRI OR
• History of carotid revascularization (stent or bypass) OR
• History of peripheral arterial disease requiring revascularization (stent or bypass; Fontaine IV)
• Aortic disease that required a vascular repair or aortic aneurysm with a maximum diameter \>5.5 cm (men) or \>5.2 cm (women) based on available documents
• Diagnosis of familial hypercholesterolemia based on Dutch lipid score ≥6 based on available documents (LDL-c, Family History, Personal History)
• Elevated risk of death within 3 months after baseline, defined as:
• Hospitalized patients planned for palliative care within 24h of admission OR
• Hospitalized patients with a Palliative Performance Scale (PPS) level \<30% (based on situation at least 1 month before hospitalization), this corresponds to an estimated survival of 43% after 3 months; OR
• Patients with an advanced metastatic cancer prognosis of ≤20% survival rate within 1 year after baseline (based on an online tool: https://cancersurvivalrates.com)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• University of Bern: collaborator

Study Sites (1)

University Hospital of Bern, University of Bern

Bern, 3010, Switzerland

RECRUITING

Study Officials

• Manuel R Blum, MD, MSc

  University Hospital of Bern, University of Bern, Switzerland; Institute of Primary Health Care, University of Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manuel R Blum, MD, MSc

CONTACT

+41 31 632 21 11; manuel.blum@insel.ch

Nicolas Rodondi, MD, MAS

CONTACT

+41 31 632 00 69; nicolas.rodondi@insel.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The study is open-label, with blinded outcome adjudication. Identification of potential outcome events is performed by blinded study team members. Participants, care providers, investigators and outcomes assessors are blinded to the baseline biomarker levels.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: August 1, 2022
• Study Start: November 21, 2022
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: November 30, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Foreseen for one year after publication of the main trial results. Items will be retained indefinitely.
• Access Criteria: All efforts will be made to protect privacy and to de-identify the data. However, datasets contain sensitive data. Therefore, data will be shared on request under the following conditions: * A meaningful study question by the requester * Outline of the planned analyses * Valid methodology Signed data sharing agreement that contains a confidentiality agreement and other obligations to ensure privacy of trial participants

Locations

CH (1)