Statin Treatment for Primary PreventionSTREAM-BioNCT05482386
STREAM Trial - Biomarker
A study testing Statin discontinuation in people with Statin Treatment for Primary Prevention, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Statin Treatment for Primary Prevention
- What is being tested?
- Statin discontinuation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 1 siteSwitzerland
- Study dates
- 21 Nov 2022to Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- ≥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
Who cannot join
- 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
Show all 15Show fewer
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
University Hospital of Bern, University of Bern
Bern, 3010
Manuel R Blum, MD, MSc, +41 31 632 00 69, manuel.blum@insel.ch
Manuel R Blum, MD, MSc
About this study
Official title: Utility of Biomarkers With Statin Therapy in Multimorbid Older Adults - An Ancillary Study Nested Within a Randomized Trial
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.
Read the detailed description
Background \& rationale: The benefit of statin use for primary prevention is uncertain in older adults with multimorbidity, while harms such as side effects may be more common in this population. Therefore, the 2018 AHA/ACC cholesterol guidelines mention that it may be reasonable to discontinue statins in multimorbid older adults without cardiovascular disease (CVD). 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 this question, 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.
Specific aim:
To determine if the risk of a composite outcome of CV events and all-cause mortality after statin discontinuation differs according to the baseline levels of previously validated blood biomarkers associated with increased risk of CV outcomes (lipoprotein(a), inflammatory markers [high-sensitivity C-reactive Protein], myocardial damage/wall strain [NT-proBNP, troponin]).
Design:
The study is a multicenter, randomized, non-inferiority trial conducted in multiple centers in Switzerland. Study subjects are randomly assigned in a 1:1 ratio to either discontinue (intervention arm) or continue (control arm) statin therapy. The study is open-label, with blinded outcome adjudication. After inclusion the study participants will be followed with phone calls, first after 3 months and then yearly for a mean of 24 months (min. follow-up period 12 months, max. follow-up period 48 months). Outcomes are assessed at each study follow-up. We will measure previously validated biomarkers at baseline.
- Conditions
- Statin Treatment for Primary Prevention
- Being tested
- Statin discontinuation
- Keywords
- Cardiovascular biomarkers, Statins, Primary prevention, Multimorbidity, Older adults
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Statin discontinuationOther
Also called Intervention arm
Statin therapy will be stopped. Additional lipid-lowering medication lowering LDL cholesterol will also be stopped.
| Study group | Role | What they receive |
|---|---|---|
| Statin discontinuation | Experimental | Discontinuation of statin therapy - statin therapy will be stopped from the next scheduled intake after study inclusion (intervention arm). Receives: Other: Statin discontinuation |
| Statin continuation | No intervention | Continuation of statin therapy - no change in the prescribed statin therapy (control arm). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 48 months
Secondary outcomes (10)
All-cause death
All deaths (for any reason)
Measured: Up to 48 months
Non-CV death
All deaths except of deaths due to major CV events
Measured: Up to 48 months
Major CV events
CV death, non-fatal myocardial infarction and non-fatal ischemic stroke
Measured: Up to 48 months
Total CV events
CV death, non-fatal myocardial infarction, hospitalization for unstable angina, non-fatal ischemic stroke (including TIA) and arterial revascularization (coronary and peripheral urgent and non-urgent revascularization)
Measured: Up to 48 months
Total composite events
All-cause death, non-fatal myocardial infarction, hospitalization for unstable angina, non-fatal ischemic stroke (including TIA) and arterial revascularization (coronary and peripheral urgent and non-urgent revascularization)
Measured: Up to 48 months
EQ-5D questionnaire
EQ-5D is the name of the instrument and not an acronym. General quality of life assessment. The possible range of scores goes from 0 to 1.0, with higher scores indicating better quality of life.
Measured: 3, 12 (primary analysis), 24, 36, 48 months
Verbal numeric pain rating score (VNPRS)
To assess statin associated muscle symptoms. The VNPRS is an 11-point scale scored from 0-10, with higher scores indicating higher degree of pain.
Measured: 3 months
Self-reported falls
Self-reported falls, each participant will collect and list all falls during the first 12 months after randomization. Circumstances and medical consequences of each fall will be collected. Aggregated as rate of falls (falls per person per year).
Measured: Up to 12 months
Strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F questionnaire)
5-item questionnaire, the score ranges from 0 to 10 with higher scores indicating higher degree of sarcopenia.
Measured: 12 (primary analysis), 24, 36, 48 months
Girerd medication adherence scale
6-item questionnaire, the score ranges from 0 to 6, higher scores indicating worse medication adherence.
Measured: 12 (primary analysis), 24, 36, 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2022
- Study start21 Nov 2022
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Statin Treatment for Primary PreventionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bern
- Responsible party
- Sponsor
- Investigators
- Manuel R Blum, MD, MSc, Principal investigator, University Hospital of Bern, University of Bern, Switzerland; Institute of Primary Health Care, University of Bern, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05482386
- Sponsor's protocol ID
- STREAM-Biomarker
- Other IDs
- 32003B_205067, FF21106
- Acronym
- STREAM-Bio
- Status last verified
- Nov 2023
- First submitted
- 28 Jul 2022
- Last updated
- 30 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be deposited in the BORIS Research Data, the research data repository of the University of Bern. BORIS Research Data allows searching and is indexed by search engines. All items are stored with a unique Digital Object Identifier (DOI) that can be referenced in respective publication. It should be noted that the investigators plan to register and deposit data that relates to individual, primary publications and not the whole study database as such, as the investigators will use them for secondary analysis. This enables other researchers to replicate published analyses and results as well as to re-use the data for additional analyses such as metaanalysis. It is planned to disseminate the results of the trial to key target groups using the Lavis' framework for research knowledge transfer
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Utility of Biomarkers With Statin Therapy in Multimorbid Older Adults - An Ancillary Study Nested Within a Randomized Trial
- ClinicalTrials.gov ID
- NCT05482386
- Acronym / sponsor ID
- STREAM-Bio / STREAM-Biomarker
- Conditions
- Statin Treatment for Primary Prevention
- Keywords
- Cardiovascular biomarkers, Statins, Primary prevention, Multimorbidity, Older adults
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- University of Bern
- Study start
- 21 Nov 2022 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 1 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background \& rationale: The benefit of statin use for primary prevention is uncertain in older adults with multimorbidity, while harms such as side effects may be more common in this population. Therefore, the 2018 AHA/ACC cholesterol guidelines mention that it may be reasonable to discontinue statins in multimorbid older adults without cardiovascular disease (CVD). 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 this question, 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.
Specific aim:
To determine if the risk of a composite outcome of CV events and all-cause mortality after statin discontinuation differs according to the baseline levels of previously validated blood biomarkers associated with increased risk of CV outcomes (lipoprotein(a), inflammatory markers [high-sensitivity C-reactive Protein], myocardial damage/wall strain [NT-proBNP, troponin]).
Design:
The study is a multicenter, randomized, non-inferiority trial conducted in multiple centers in Switzerland. Study subjects are randomly assigned in a 1:1 ratio to either discontinue (intervention arm) or continue (control arm) statin therapy. The study is open-label, with blinded outcome adjudication. After inclusion the study participants will be followed with phone calls, first after 3 months and then yearly for a mean of 24 months (min. follow-up period 12 months, max. follow-up period 48 months). Outcomes are assessed at each study follow-up. We will measure previously validated biomarkers at baseline.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Statin discontinuation | Experimental | Other: Statin discontinuationDiscontinuation of statin therapy - statin therapy will be stopped from the next scheduled intake after study inclusion (intervention arm). |
| Statin continuation | No intervention | –Continuation of statin therapy - no change in the prescribed statin therapy (control arm). |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- ≥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
Key exclusion criteria (15 listed)
- Secondary prevention based on previous large statin trials, defined as:
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Statin discontinuationAlso: Intervention armStatin therapy will be stopped. Additional lipid-lowering medication lowering LDL cholesterol will also be stopped. | Other | Statin discontinuation |
Primary outcome
Composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke)
Time frame: Up to 48 months
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.
10 secondary outcomes
All-cause death
Time frame: Up to 48 months
Non-CV death
Time frame: Up to 48 months
Major CV events
Time frame: Up to 48 months
Total CV events
Time frame: Up to 48 months
Total composite events
Time frame: Up to 48 months
EQ-5D questionnaire
Time frame: 3, 12 (primary analysis), 24, 36, 48 months
Verbal numeric pain rating score (VNPRS)
Time frame: 3 months
Self-reported falls
Time frame: Up to 12 months
Strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F questionnaire)
Time frame: 12 (primary analysis), 24, 36, 48 months
Girerd medication adherence scale
Time frame: 12 (primary analysis), 24, 36, 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2023.
- Individual participant dataSharing planned: Yes. Data will be deposited in the BORIS Research Data, the research data repository of the University of Bern. BORIS Research Data allows searching and is indexed by search engines. All items are stored with a unique Digital Object Identifier (DOI) that can be referenced in respective publication. It should be noted that the investigators plan to register and deposit data that relates to individual, primary publications and not the whole study database as such, as the investigators will use them for secondary analysis. This enables other researchers to replicate published analyses and results as well as to re-use the data for additional analyses such as metaanalysis. It is planned to disseminate the results of the trial to key target groups using the Lavis' framework for research knowledge transfer
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Manuel R Blum, MD, MSc principal investigator
University Hospital of Bern, University of Bern, Switzerland; Institute of Primary Health Care, University of Bern, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Statin discontinuation in people with Statin Treatment for Primary Prevention, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Manuel R Blum, MD, MSc (+41 31 632 21 11 ext. 8008, manuel.blum@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke) (time frame: Up to 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2023.