Heart Failure, DiastolicPhase 3OPTIMIZE-HFPEFNCT02425371
Optimized Management of Comorbidity in Heart Failure With Preserved Ejection Fraction in the Elderly (>60 Years)
A Phase 3 study testing Screening and treatment of comorbidities in people with Heart Failure, Diastolic, run by Göteborg University at 1 site in Sweden.
Trial summary
Growing recognition of the importance of co-morbidities in Heart Failure with Preserved Ejection Fraction (HFPEF) has led to the realization that rather than being a distinct disease entity, HFPEF may represent a spectrum of co-morbidities in elderly breathless patients. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Heart Failure, Diastolic
- What is being tested?
- Screening and treatment of comorbidities
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 410 participants
- Where
- 1 siteSweden
- Study dates
- Sep 2014to Jul 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Validated HFPEF
- Age >60 years
- Chronic Heart Failure with at least one hospitalization or increased use of diuretics due to worsening is required during the last year
- New York Heart Association class II -IV
- Regarded as optimally treated and stable for at least 4 weeks (physician's opinion)
Who cannot join
- Currently enrolled in another study
- Significant chronic obstructive pulmonary disease (COPD) with forced expiratory volume within one second (FEV1) < 30% (European Respiratory Society criteria) in the last 4 weeks before randomization
- Glomerular filtration rate (GFR) <30 ml/min/1.73m2 (Modification of Diet in Renal Disease [MDRD] GFR Equation)
- Significant primary valve disease
- Body mass index (BMI) >40
- Severe cognitive dysfunction or dementia
- Expected survival of less than one year
- Planned cardiac surgery, Percutaneous Coronary Intervention
Trial locations and contacts
1 site in 1 country.
Sweden1 site, 1 recruiting
- Recruiting
Dept. Medicine
Gothenburg, Vastragotaland, 41345
Michael X Fu, Professor, +46 31343434850, michael.fu@vgregion.se
Erik Thunstrom, MD, +46313434813, erik.thunstrom@vgregion.se
About this study
Official title: Optimized Management of Comorbidity in Heart Failure With Preserved Ejection Fraction in the Elderly (>60 Years) (OPTIMIZE-HFPEF)
Growing recognition of the importance of co-morbidities in Heart Failure with Preserved Ejection Fraction (HFPEF) has led to the realization that rather than being a distinct disease entity, HFPEF may represent a spectrum of co-morbidities in elderly breathless patients. Accordingly, progress in managing HFPEF in the elderly requires improved understanding of HFPEF pathogenesis with a focus on the impact of co-morbidities. However, the available evidence is insufficient to determine the true prevalence and severity of co-morbidities as well as their impact on both diagnosis and treatment in HFPEF. Therefore there are widespread diagnostic uncertainty without proven therapy!
The purpose of this project is twofold:
Read more
- The investigators will study how to improve diagnostic accuracy for HFPEF in elderly patients, despite frequent comorbidities and higher age? How useful is it to add exercise testing and contrast echocardiography as well as biomarker as additional diagnostic tools in elderly HFPEF patients?
- The investigators will test the hypothesis that HFPEF in the elderly is dominated by multiple co-morbidities that are a major part of the syndrome itself that contribute to the development of HFPEF. This hypothesis implies that the treatment of co-morbidities will improve prognosis.
The investigators' overall goal is to bring about a paradigm shift in managing elderly patients with HFPEF by not only improving diagnosis but also effectively treating co-morbidities that are currently considered predisposing factors to HFPEF. This contrasts with trials during last two decades that only target the heart.
The investigators will pursue the following specific aims:
- Validate the diagnostic criteria for HFPEF proposed by European Society of Cardiology 2012, and determine the added diagnostic values of exercise testing and contrast echocardiography as well as biomarker for HFPEF in a multi-center study.
- Determine if systematic screening and optimal management of co-morbidities associated with HFPEF improves the outcomes of patients with HFPEF in a randomized study.
Read the detailed description
Heart failure is primarily a disease of the elderly, with approximately half of these cases occurring in patients aged ≥75 years. Heart failure is the leading cause of hospitalization in the elderly. Moreover, it worsens cognition, physical function and quality of life, increases health care costs and leads to higher mortality. Nearly half of the patients with heart failure have preserved ejection fraction (HFPEF), and the prevalence appears to be rising. Although patterns of morbidity and functional decline are similar in patients with HFPEF to those with heart failure and reduced ejection fraction (HFREF), HFPEF represents a particular challenge since there is no proven treatment. Therapies that are effective in HFREF, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and beta blockers, have so far been unsuccessful in HFPEF. This differential response to therapy combined with distinct patterns of structural remodeling suggests that HFPEF and HFREF are two discrete entities with fundamentally different pathophysiologies. A recently proposed mechanism for HFPEF development identifies a systemic pro-inflammatory state induced by comorbidities as the primary cause of HFPEF. Therefore, progress in managing HFPEF requires improved understanding of HFPEF pathogenesis with a focus on the impact of comorbidities.
Hypothesis: HFPEF in the elderly is dominated by multiple comorbidity which are not a complicating factor in HFPEF, but a major part of the syndrome, contribute to the HFPEF. Therefore, to make comorbidity as attractive therapeutic target will promote a paradigm shift toward individualized optimal care in elderly patients with HFPEF.
Main purpose: To promote a paradigm shift toward individualized optimal care in elderly patients with HFPEF by effective treatment of the comorbidities.
Specific aim: To determine if systematic screening and optimal management of comorbidities associated with HFPEF will improve outcome in patients with HFPEF
Work plan: The investigators' intervention study will use a multi-centre, prospective, randomized, open procedure but blinded end-point (PROBE) design. Patients (n=220) are randomized 1:1 to either usual care (n=110) or intervention (n=110). Inclusion criteria are HFPEF >60 years. In the Intervention arm, all patients will be subject to systematic screening and optimal treatment of 12 most frequently seen co-morbidity. Endpoints will be collected by Independent Endpoint Committee once a year during 2 years.
Significance and clinical relevance : The present study focuses on an important issue in the investigators' society, namely HFPEF in the elderly population. This health problem has been largely ignored despite the fact that there is no recommended therapy. The investigators' proposed study represents a paradigm shift in therapy. It is based on a new concept focusing on comorbidities that are considered to be predisposing factors to HFPEF in contrast to available trials that target only the heart. The investigators' study therefore challenges the current clinical practice and may fill the knowledge gap in HFPEF.
- Conditions
- Heart Failure, Diastolic
- Being tested
- Screening and treatment of comorbidities, Placebo Comparator
- Medical subject headings
- Heart Failure, Diastolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Screening and treatment of comorbiditiesOther
Screening and treatment of comorbidities
Placebo ComparatorOther
No screening of comorbidities
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | screening and treatment of comorbidities Receives: Other: Screening and treatment of comorbidities |
| Control | Placebo comparator | No screening of comorbidity Receives: Other: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
A composite endpoint about which includes the patient's well-being symptoms (improved or worsened)
A composite endpoint about which includes the patient's well-being symptoms (improved or worsened). The endpoint consists of 4 effect categories composites that are determined on an individual basis at baseline and at 12 months. Each effect category has to meet either all 4 main criteria (1) Lickert scale 5 levels(breathlessness); (2) Lickert scale (tiredness); (3) NT-proBNP change of 30% from baseline; and (4) any events such the occurence of deaths mortality, hospital admission for heart failure or, use of intravenous diuretics during 12 months
Measured: Change between baseline and after 2 years
Secondary outcomes (1)
All cause mortality or hospitalization
All cause mortality or hospitalization due to cardiovascular causes (time to first event); All cause mortality;
Total number of hospitalizations; The non-fatal clinical progression of heart failure, assessed subjectively by patients and physicians and objectively by the occurrence of major clinical events.
Measured: Change between baseline and after 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2015 (estimated)
- Study startSep 2014
- Primary completionMar 2019 (estimated)
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure, DiastolicStudies of the same condition, open and under way.
- More trials run by Göteborg UniversityThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 410 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Göteborg University
- Sponsor type
- University, hospital or other
- Collaborators
- Umeå University, Karolinska Institutet, Uppsala University, Vastra Gotaland Region
- Responsible party
- Sponsor
- Investigators
- Michael X Fu, Professor, Principal investigator, Göteborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02425371
- Sponsor's protocol ID
- VGFOUREG-127071
- Acronym
- OPTIMIZE-HFPEF
- Status last verified
- Sep 2018
- First submitted
- 25 Feb 2015
- Last updated
- 7 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fu M, Zhou J, Thunstrom E, Almgren T, Grote L, Bollano E, Schaufelberger M, Johansson MC, Petzold M, Swedberg K, Andersson B. Optimizing the Management of Heart Failure With Preserved Ejection Fraction in the Elderly by Targeting Comorbidities (OPTIMIZE-HFPEF). J Card Fail. 2016 Jul;22(7):539-44. doi: 10.1016/j.cardfail.2016.01.011. Epub 2016 Jan 25.
PubMed 26820355
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimized Management of Comorbidity in Heart Failure With Preserved Ejection Fraction in the Elderly (>60 Years) (OPTIMIZE-HFPEF)
- ClinicalTrials.gov ID
- NCT02425371
- Acronym / sponsor ID
- OPTIMIZE-HFPEF / VGFOUREG-127071
- Conditions
- Heart Failure, Diastolic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 410 participants (estimated)
- Lead sponsor
- Göteborg UniversityUniversity, hospital or other
- Collaborators
- Umeå University, Karolinska Institutet, Uppsala University, Vastra Gotaland Region
- Study start
- Sep 2014
- Primary completion
- Mar 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 24 Apr 2015 (estimated)
- 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.
Growing recognition of the importance of co-morbidities in Heart Failure with Preserved Ejection Fraction (HFPEF) has led to the realization that rather than being a distinct disease entity, HFPEF may represent a spectrum of co-morbidities in elderly breathless patients. Accordingly, progress in managing HFPEF in the elderly requires improved understanding of HFPEF pathogenesis with a focus on the impact of co-morbidities. However, the available evidence is insufficient to determine the true prevalence and severity of co-morbidities as well as their impact on both diagnosis and treatment in HFPEF. Therefore there are widespread diagnostic uncertainty without proven therapy!
The purpose of this project is twofold:
- The investigators will study how to improve diagnostic accuracy for HFPEF in elderly patients, despite frequent comorbidities and higher age? How useful is it to add exercise testing and contrast echocardiography as well as biomarker as additional diagnostic tools in elderly HFPEF patients?
- The investigators will test the hypothesis that HFPEF in the elderly is dominated by multiple co-morbidities that are a major part of the syndrome itself that contribute to the development of HFPEF. This hypothesis implies that the treatment of co-morbidities will improve prognosis.
The investigators' overall goal is to bring about a paradigm shift in managing elderly patients with HFPEF by not only improving diagnosis but also effectively treating co-morbidities that are currently considered predisposing factors to HFPEF. This contrasts with trials during last two decades that only target the heart.
The investigators will pursue the following specific aims:
- Validate the diagnostic criteria for HFPEF proposed by European Society of Cardiology 2012, and determine the added diagnostic values of exercise testing and contrast echocardiography as well as biomarker for HFPEF in a multi-center study.
- Determine if systematic screening and optimal management of co-morbidities associated with HFPEF improves the outcomes of patients with HFPEF in a randomized study.
Detailed description
Heart failure is primarily a disease of the elderly, with approximately half of these cases occurring in patients aged ≥75 years. Heart failure is the leading cause of hospitalization in the elderly. Moreover, it worsens cognition, physical function and quality of life, increases health care costs and leads to higher mortality. Nearly half of the patients with heart failure have preserved ejection fraction (HFPEF), and the prevalence appears to be rising. Although patterns of morbidity and functional decline are similar in patients with HFPEF to those with heart failure and reduced ejection fraction (HFREF), HFPEF represents a particular challenge since there is no proven treatment. Therapies that are effective in HFREF, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and beta blockers, have so far been unsuccessful in HFPEF. This differential response to therapy combined with distinct patterns of structural remodeling suggests that HFPEF and HFREF are two discrete entities with fundamentally different pathophysiologies. A recently proposed mechanism for HFPEF development identifies a systemic pro-inflammatory state induced by comorbidities as the primary cause of HFPEF. Therefore, progress in managing HFPEF requires improved understanding of HFPEF pathogenesis with a focus on the impact of comorbidities.
Hypothesis: HFPEF in the elderly is dominated by multiple comorbidity which are not a complicating factor in HFPEF, but a major part of the syndrome, contribute to the HFPEF. Therefore, to make comorbidity as attractive therapeutic target will promote a paradigm shift toward individualized optimal care in elderly patients with HFPEF.
Main purpose: To promote a paradigm shift toward individualized optimal care in elderly patients with HFPEF by effective treatment of the comorbidities.
Specific aim: To determine if systematic screening and optimal management of comorbidities associated with HFPEF will improve outcome in patients with HFPEF
Work plan: The investigators' intervention study will use a multi-centre, prospective, randomized, open procedure but blinded end-point (PROBE) design. Patients (n=220) are randomized 1:1 to either usual care (n=110) or intervention (n=110). Inclusion criteria are HFPEF >60 years. In the Intervention arm, all patients will be subject to systematic screening and optimal treatment of 12 most frequently seen co-morbidity. Endpoints will be collected by Independent Endpoint Committee once a year during 2 years.
Significance and clinical relevance : The present study focuses on an important issue in the investigators' society, namely HFPEF in the elderly population. This health problem has been largely ignored despite the fact that there is no recommended therapy. The investigators' proposed study represents a paradigm shift in therapy. It is based on a new concept focusing on comorbidities that are considered to be predisposing factors to HFPEF in contrast to available trials that target only the heart. The investigators' study therefore challenges the current clinical practice and may fill the knowledge gap in HFPEF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: Screening and treatment of comorbiditiesscreening and treatment of comorbidities |
| Control | Placebo comparator | Other: Placebo ComparatorNo screening of comorbidity |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Validated HFPEF
- Age >60 years
- Chronic Heart Failure with at least one hospitalization or increased use of diuretics due to worsening is required during the last year
- New York Heart Association class II -IV
- Regarded as optimally treated and stable for at least 4 weeks (physician's opinion)
Key exclusion criteria (8 listed)
- Currently enrolled in another study
- Significant chronic obstructive pulmonary disease (COPD) with forced expiratory volume within one second (FEV1) < 30% (European Respiratory Society criteria) in the last 4 weeks before randomization
- Glomerular filtration rate (GFR) <30 ml/min/1.73m2 (Modification of Diet in Renal Disease [MDRD] GFR Equation)
- Significant primary valve disease
- Body mass index (BMI) >40
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 |
|---|---|---|
| Screening and treatment of comorbiditiesScreening and treatment of comorbidities | Other | Intervention |
| Placebo ComparatorNo screening of comorbidities | Other | Control |
Primary outcome
A composite endpoint about which includes the patient's well-being symptoms (improved or worsened)
Time frame: Change between baseline and after 2 years
A composite endpoint about which includes the patient's well-being symptoms (improved or worsened). The endpoint consists of 4 effect categories composites that are determined on an individual basis at baseline and at 12 months. Each effect category has to meet either all 4 main criteria (1) Lickert scale 5 levels(breathlessness); (2) Lickert scale (tiredness); (3) NT-proBNP change of 30% from baseline; and (4) any events such the occurence of deaths mortality, hospital admission for heart failure or, use of intravenous diuretics during 12 months
1 secondary outcome
All cause mortality or hospitalization
Time frame: Change between baseline and after 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2018.
- Background: PubMed 26820355Fu M, Zhou J, Thunstrom E, Almgren T, Grote L, Bollano E, Schaufelberger M, Johansson MC, Petzold M, Swedberg K, Andersson B. Optimizing the Management of Heart Failure With Preserved Ejection Fraction in the Elderly by Targeting Comorbidities (OPTIMIZE-HFPEF). J Card Fail. 2016 Jul;22(7):539-44. doi: 10.1016/j.cardfail.2016.01.011. Epub 2016 Jan 25.
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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. This study is not recruiting at the moment.
Michael X Fu, Professor principal investigator
Göteborg University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Screening and treatment of comorbidities in people with Heart Failure, Diastolic, run by Göteborg University at 1 site in Sweden.
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 5 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 7 Sep 2018. 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 Sweden. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael Fu, Professor (0046(0)31 3421000, michael.fu@vgregion.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A composite endpoint about which includes the patient's well-being symptoms (improved or worsened) (time frame: Change between baseline and after 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02425371, which also lists 1 linked publication.
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 7 Sep 2018.