Heart FailureIMPULSE-HFNCT02857309
Cardiac Contractility Modulation (CCM) Therapy in Subjects With Medically Refractory Heart Failure
A study testing OPTIMIZER and Optimal medical therapy in people with Heart Failure, run by Impulse Dynamics at 8 sites in 4 countries.
Trial summary
The study is designed to substantiate the efficacy of Cardiac Contractility Modulation (CCM) in the heart failure population with ejection fraction ranging between 25 and 45%. The study is designed in an adaptive manner to ensure proper statistical significance and power of the primary efficacy evaluation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- OPTIMIZER and Optimal medical therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 8 sitesin 4 countries
- Study dates
- Feb 2014to 15 Feb 2018
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Baseline ejection fraction ≥ 25% and ≤45% (as assessed by the site)
- NYHA class II or III (chronic, not transient, heart failure) despite receiving optimal medical therapy for heart failure
- Stable medication for heart failure for at least 30 days based on patient's medical records
- Baseline Peak VO2 ≥ 10 and ≤ 18.5 ml O2/Kg/min (as assessed by the site)
Who cannot join
- Potentially correctible cause of HF (valvular, congenital, or untreated ischemic heart disease)
- Clinically significant angina pectoris
- Hospitalization for HF requiring the use of inotropic support or IV diuretics within 30 days of enrollment
- PR interval greater than 375 ms
- Permanent or persistent atrial fibrillation/flutter or cardioversion within 30 days of enrollment.
- Exercise tolerance limited by condition other than heart failure (e.g., angina, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, orthopedic or rheumatologic conditions) or unable to perform baseline stress testing
Show all 16Show fewer
- Scheduled for a coronary artery bypass graft (CABG) or a percutaneous transluminal coronary angioplasty (PTCA) procedure, or CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment.
- Biventricular pacing system, or indication for Biventricular pacing system
- Myocardial infarction within 90 days of enrollment.
- Mechanical tricuspid or aortic valves.
- Ventricular assist device
- Prior heart transplant
- Pregnant or planning to become pregnant during the study
- Age below 18
- Subject participating in another study, unrelated to CCM, at the same time (or within 30 days prior to enrollment to this study)
- Subjects on dialysis
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
Germany5 sites
Universtitätsklinikum; Medizinische Klinik I
Aachen
Universitätsklinikum; Kardiologie im Herzzentrum
Cologne
Helios Klinikum; 3. Medizinische Klinik
Erfurt
Albertinen Krankenhaus
Hamburg
Universität Leipzig; Abteilung für Kardiologie und Angiologie
Leipzig
About this study
Official title: Cardiac Contractility Modulation (CCM) Therapy in Subjects With Medically Refractory Heart Failure: A Randomized Efficacy Study
The study is designed to substantiate the efficacy of Cardiac Contractility Modulation (CCM) in the heart failure population with ejection fraction ranging between 25 and 45%. The study is designed in an adaptive manner to ensure proper statistical significance and power of the primary efficacy evaluation.
Read the detailed description
This study will collect efficacy data in a randomized controlled setting, including New York Heart Association (NYHA) class II and III Heart Failure population with baseline ejection fraction (EF) of 25% to 45%.
There is previous evidence related to the beneficial effect of CCM in patients with baseline ejection fraction of <35%. While patients with EF between 35% and 45% were not prospectively studied in the original clinical study initially conducted to support Conformité Européene (CE) Marking of the OPTIMIZER System, recently available data from a randomized study that included such patients show CCM to be safe and effective in this group of patients as well. Furthermore, the literature supports that this population has very similar clinical characteristics, in practice are treated with nearly the same medications, and have similar underlying mechanisms of disease compared to patients with EF <35%. CCM has been successfully used also in patients with EF greater than 35% in routine use and in the FIX-HF-5 study.
Since the system is CE marked and since the population includes patients meeting the approved indication as well as population that has shown to benefit from CCM (EF 35%-45%), the risk involved in performing such a clinical investigation seems acceptable.
The study is designed to substantiate the efficacy of CCM in heart failure patients with EFs in the range of 25%-to-45% (inclusive). This is a prospective, randomized study comparing CCM plus optimal medical therapy (OMT) (Treatment Group) to OMT alone (Control Group) over a 24 week period. The primary endpoint shall be a comparison of changes in Peak VO2, which is an established objective physiological indicator of exercise capacity which is relevant in heart failure device studies. To further improve the accuracy and objectivity of measurements, double assessment of the Peak VO2 will be performed at each of the primary time points. Tests can be performed using upright and semi-supine bicycle ergometer or using treadmill. In sites where more than one option is available, bicycle ergometer is the preferred option. Treadmill is only allowed in case no bicycle is available at the site. Each subject shall be consistently tested using the same method throughout the study. The study is designed in an adaptive manner to ensure proper statistical significance and power of the primary efficacy evaluation.
The study will collect additional (exploratory) efficacy data on the difference between the treatment group and control group in the changes over 24 weeks in predicted survival probability. To evaluate the survival probability, two established models are used: the Seattle Heart Failure Model (SHFM), and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) model . These models use information collected at a certain time point to predict survival probabilities over the following years. The information used for such prediction includes status of the disease (NYHA, Left Ventricular EF (LVEF)), documented medical history and co-morbidities, documented therapies and medications, and standard blood tests values.
Additionally, hospitalization data will be collected from medical records of the site and/or from any other medical records of clinics/hospitals where the patient may have been treated for a timeframe of 12 months before enrollment and until 24 weeks after the Study Start Date (SSD).
- Conditions
- Heart Failure
- Being tested
- OPTIMIZER, Optimal medical therapy
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPTIMIZERDevice
The OPTIMIZER System delivers non-excitatory cardiac contractility modulation (CCM) signals to the heart that are intended to influence myocardial properties in patients with chronic heart failure. The system has no pacemaker or implantable cardioverter-defibrillator (ICD) functions.
Optimal medical therapyDrug
Also called angiotensin receptor blockers, mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitors
OMT using standard heart failure (HF) drugs
| Study group | Role | What they receive |
|---|---|---|
| Device implant | Other | Patients randomized to the treatment group will receive optimal medical therapy for heart failure. and implantation of the OPTIMIZER System. Receives: Device: OPTIMIZER; Drug: Optimal medical therapy |
| Optimal medical therapy | Active comparator | Patients randomized to the control group will receive optimal medical therapy for heart failure. Receives: Drug: Optimal medical therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison between the groups of the change in Peak VO2 from baseline to 24 weeks of follow-up.
Measured: from baseline to 24 weeks of follow-up
Secondary outcomes (3)
Comparison of change in quality of life as measure (MLWHFQ), from baseline to 24 weeks of follow-up
Measured: from baseline to 24 weeks of follow-up
Comparison of change in NYHA class, from baseline to 24 weeks of follow-up
Measured: from baseline to 24 weeks of follow-up
Comparison of change in Peak VO2 from baseline to 24 weeks of follow-up for each of the following subgroups separately: Baseline EF <35% , baseline EF ≥35%
Measured: from baseline to 24 weeks of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2016 (estimated)
- Study startFeb 2014
- Primary completion15 Feb 2018
- Study completion15 Feb 2018
Why it stopped: Slow enrolment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies 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
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Impulse Dynamics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gerhard Hindricks, Prof., Principal investigator, Herzzentrum Leipzig GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02857309
- Sponsor's protocol ID
- ID_CP_OPT2013-026
- Acronym
- IMPULSE-HF
- Status last verified
- Sep 2020
- First submitted
- 20 Jul 2016
- Last updated
- 2 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Contractility Modulation (CCM) Therapy in Subjects With Medically Refractory Heart Failure: A Randomized Efficacy Study
- ClinicalTrials.gov ID
- NCT02857309
- Acronym / sponsor ID
- IMPULSE-HF / ID_CP_OPT2013-026
- Conditions
- Heart Failure
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrolment.
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Impulse DynamicsIndustry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- 15 Feb 2018 (actual)
- Study completion
- 15 Feb 2018 (actual)
- First posted
- 5 Aug 2016 (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.
The study is designed to substantiate the efficacy of Cardiac Contractility Modulation (CCM) in the heart failure population with ejection fraction ranging between 25 and 45%. The study is designed in an adaptive manner to ensure proper statistical significance and power of the primary efficacy evaluation.
Detailed description
This study will collect efficacy data in a randomized controlled setting, including New York Heart Association (NYHA) class II and III Heart Failure population with baseline ejection fraction (EF) of 25% to 45%.
There is previous evidence related to the beneficial effect of CCM in patients with baseline ejection fraction of <35%. While patients with EF between 35% and 45% were not prospectively studied in the original clinical study initially conducted to support Conformité Européene (CE) Marking of the OPTIMIZER System, recently available data from a randomized study that included such patients show CCM to be safe and effective in this group of patients as well. Furthermore, the literature supports that this population has very similar clinical characteristics, in practice are treated with nearly the same medications, and have similar underlying mechanisms of disease compared to patients with EF <35%. CCM has been successfully used also in patients with EF greater than 35% in routine use and in the FIX-HF-5 study.
Since the system is CE marked and since the population includes patients meeting the approved indication as well as population that has shown to benefit from CCM (EF 35%-45%), the risk involved in performing such a clinical investigation seems acceptable.
The study is designed to substantiate the efficacy of CCM in heart failure patients with EFs in the range of 25%-to-45% (inclusive). This is a prospective, randomized study comparing CCM plus optimal medical therapy (OMT) (Treatment Group) to OMT alone (Control Group) over a 24 week period. The primary endpoint shall be a comparison of changes in Peak VO2, which is an established objective physiological indicator of exercise capacity which is relevant in heart failure device studies. To further improve the accuracy and objectivity of measurements, double assessment of the Peak VO2 will be performed at each of the primary time points. Tests can be performed using upright and semi-supine bicycle ergometer or using treadmill. In sites where more than one option is available, bicycle ergometer is the preferred option. Treadmill is only allowed in case no bicycle is available at the site. Each subject shall be consistently tested using the same method throughout the study. The study is designed in an adaptive manner to ensure proper statistical significance and power of the primary efficacy evaluation.
The study will collect additional (exploratory) efficacy data on the difference between the treatment group and control group in the changes over 24 weeks in predicted survival probability. To evaluate the survival probability, two established models are used: the Seattle Heart Failure Model (SHFM), and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) model . These models use information collected at a certain time point to predict survival probabilities over the following years. The information used for such prediction includes status of the disease (NYHA, Left Ventricular EF (LVEF)), documented medical history and co-morbidities, documented therapies and medications, and standard blood tests values.
Additionally, hospitalization data will be collected from medical records of the site and/or from any other medical records of clinics/hospitals where the patient may have been treated for a timeframe of 12 months before enrollment and until 24 weeks after the Study Start Date (SSD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Device implant | Other | Device: OPTIMIZER, Drug: Optimal medical therapyPatients randomized to the treatment group will receive optimal medical therapy for heart failure. and implantation of the OPTIMIZER System. |
| Optimal medical therapy | Active comparator | Drug: Optimal medical therapyPatients randomized to the control group will receive optimal medical therapy for heart failure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Baseline ejection fraction ≥ 25% and ≤45% (as assessed by the site)
- NYHA class II or III (chronic, not transient, heart failure) despite receiving optimal medical therapy for heart failure
- Stable medication for heart failure for at least 30 days based on patient's medical records
- Baseline Peak VO2 ≥ 10 and ≤ 18.5 ml O2/Kg/min (as assessed by the site)
Key exclusion criteria (16 listed)
- Potentially correctible cause of HF (valvular, congenital, or untreated ischemic heart disease)
- Clinically significant angina pectoris
- Hospitalization for HF requiring the use of inotropic support or IV diuretics within 30 days of enrollment
- PR interval greater than 375 ms
- Permanent or persistent atrial fibrillation/flutter or cardioversion within 30 days of enrollment.
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 |
|---|---|---|
| OPTIMIZERThe OPTIMIZER System delivers non-excitatory cardiac contractility modulation (CCM) signals to the heart that are intended to influence myocardial properties in patients with chronic heart failure. The system has no pacemaker or implantable cardioverter-defibrillator (ICD) functions. | Device | Device implant |
| Optimal medical therapyAlso: angiotensin receptor blockers, mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitorsOMT using standard heart failure (HF) drugs | Drug | Device implant, Optimal medical therapy |
Primary outcome
Comparison between the groups of the change in Peak VO2 from baseline to 24 weeks of follow-up.
Time frame: from baseline to 24 weeks of follow-up
3 secondary outcomes
Comparison of change in quality of life as measure (MLWHFQ), from baseline to 24 weeks of follow-up
Time frame: from baseline to 24 weeks of follow-up
Comparison of change in NYHA class, from baseline to 24 weeks of follow-up
Time frame: from baseline to 24 weeks of follow-up
Comparison of change in Peak VO2 from baseline to 24 weeks of follow-up for each of the following subgroups separately: Baseline EF <35% , baseline EF ≥35%
Time frame: from baseline to 24 weeks of follow-up
Results and safety
The study was stopped early (reason given: Slow enrolment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2020.
- Individual participant dataSharing planned: No
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HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
Active, not recruiting
Heart Failure Patient Management and Interventions Using Continuous Patient Monitoring Outside Hospitals and Real-world Data
Chronic Heart Failure, Heart Transplant Recipient
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Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
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Not yet recruitingObservational study
Real-world Effectiveness and Safety of Savagen (Sacubitril/Valsartan) in Malaysian HFrEF Patients
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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.
Gerhard Hindricks, Prof. principal investigator
Herzzentrum Leipzig GmbH
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing OPTIMIZER and Optimal medical therapy in people with Heart Failure, run by Impulse Dynamics at 8 sites in 4 countries.
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 4 inclusion and 16 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: stopped early, as of the sponsor's last update on 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany, Austria, Poland, 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. 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?
The study was stopped early (reason given: Slow enrolment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison between the groups of the change in Peak VO2 from baseline to 24 weeks of follow-up. (time frame: from baseline to 24 weeks of follow-up). 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 2 Sep 2020.