Heart Failure With Preserved Ejection FractionNCT03715543
Surgical Resection of the Greater Splanchnic Nerve in Subjects Having Heart Failure With Preserved Ejection Fraction
A study testing Surgical Resection of the Greater Splanchnic Nerve in people with Heart Failure With Preserved Ejection Fraction, run by Noblewell at 2 sites in 2 countries.
Trial summary
We believe that blocking of the Greater Splanchnic Nerve (GSN) will stop Sympathetic Nervous System (SNS) activity from reaching the splanchnic vessels and result in a redistribution of blood volume back into the splanchnic reservoir, which will result in reduction of central venous, pulmonary and right and left heart… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Surgical Resection of the Greater Splanchnic Nerve
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Aug 2016to 30 Jun 2019
- 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
- Adult patients ≥ 18 years of age with guideline defined HFpEF class III/IV (EF>40% on optimal medical therapy)
- History of exertion-related dyspnea in last 3 months
- No evidence of clinically significant peripheral edema/fluid overload
- Resting PCWP or PAD > 15 mmHg or > 25 mmHg during exercise
- The ability understand and provide signed informed consent
Who cannot join
- Myocardial infarction and/or percutaneous cardiac intervention within past 3 months; coronary artery bypass graft in past 3 months or current indication for coronary revascularization
- Admission for HF within the past month
- Systolic Blood Pressure (BP) < 120 mmHg or > 170 mmHg despite appropriate medical management
- Inability to perform Cardio Pulmonary Exercise Test (CPET)
- Presence of severe regurgitant or stenotic valve disease
- Atrial fibrillation with resting heart rate >100 beats/min
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- Arterial oxygen saturation < 90 % on room air
- Significant hepatic impairment, defined as 3× upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase
- Known pre-existing severe pulmonary hypertension
- Chronic pulmonary disease requiring home O2, hospitalization for exacerbation within 6 months before study entry, or on chronic steroids
- Life expectancy <12 months for non-cardiovascular reasons
- Women of childbearing age
- Currently requiring dialysis or estimated glomerular filtration rate < 40 mL/min/1.73m2
- Patients who have had cardiac transplantation or maybe considered for heart transplant
- Currently participating in an investigational drug or device study. Note: trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered to be investigational trials
- Chronic or parenteral anticoagulation drug use without ability to hold for at least 72 hours
- In the opinion of the investigator, the subject is not an appropriate candidate for the study
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Surgical Resection of the Greater Splanchnic Nerve in Subjects Having Heart Failure With Preserved Ejection Fraction: First-in-human Feasibility Trial
We believe that blocking of the Greater Splanchnic Nerve (GSN) will stop Sympathetic Nervous System (SNS) activity from reaching the splanchnic vessels and result in a redistribution of blood volume back into the splanchnic reservoir, which will result in reduction of central venous, pulmonary and right and left heart pressures. For patients having Heart Failure With Preserved Ejection Fraction (HFpEF) we expect these changes to improve dyspnea and capacity to exercise, improve quality of life, increased diuretic responsiveness, Furthermore, the expected benefits of unloading the central venous and arterial system through GSN ablation should improve hemodynamic control and lessen the incidence and severity of acute decompensations leading to reduced re-hospitalizations and associated healthcare costs. This has the potential for significant social and healthcare impact.
Read the detailed description
Heart failure (HF) is a major and growing public health problem with more than 5 million identified cases and an incidence of over 600,000 new cases per year in the United States alone. Close to 1 million hospitalizations for heart failure occur annually, accounting for over 6.5 million hospital days and a substantial portion of the estimated $37.2 billion that is spent each year on HF in the United States. Nearly half of all patients with HF have so called heart failure with preserved ejection fraction (HFpEF). The 5-year mortality for HFpEF has been reported as high as 50-65%. There are no current evidenced-based HFpEF therapies beyond diuretic control for fluid overload and standard treatments for comorbidities, making HFpEF an exemplary example of an unmet medical need of a rising societal burden and that is associated with substantial morbidity and mortality.
In HFpEF, sympathetic nervous system (SNS) hyperactivity results in decreased splanchnic capacitance causing more blood to be distributed into the central venous and arterial system. This leads to increase central venous pressure, pulmonary pressures and right/left heart pressures, which ultimately results in: congestions, diuretic resistance, acute decompensations leading to rehospitalization, dyspnea and intolerance to even mild exercise, and progressive diastolic dysfunction.
We believe that blocking of the GSN will stop SNS activity from reaching the splanchnic vessels and result in a redistribution of blood volume back into the splanchnic reservoir, which will result in reduction of central venous, pulmonary and right and left heart pressures. For patients with HFpEF we expect these changes to improve dyspnea and capacity to exercise, improve quality of life, increased diuretic responsiveness, Furthermore, the expected benefits of unloading the central venous and arterial system through GSN ablation should improve hemodynamic control and lessen the incidence and severity of acute decompensations leading to reduced re-hospitalizations and associated healthcare costs. This has the potential for significant social and healthcare impact.
Sympathetic and parasympathetic innervation is carried to the upper abdominal viscera by the GSN, lesser splanchnic nerve (LSN) and least splanchnic nerve (LTSN), which originate from the 5th to 8th, 9th to 10th, and 11th thoracic ganglia, respectively.
- Being tested
- Surgical Resection of the Greater Splanchnic Nerve
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical Resection of the Greater Splanchnic NerveProcedure or surgery
Video-Assisted Thoracoscopic Surgery (VATS) is performed under general anesthesia using existing, CE marked instrumentation. Two or more 5 mm incisions are used to pass a tiny video camera and a single dissecting instrument into the chest. These small ports are advantageous because the chance for infection and wound dehiscence are drastically reduced. This allows for a faster recovery by the patient and a greater chance for the wound to heal.
In the procedure the GSN will be identified visually or through stimulation-induced hemodynamic reflex. The GSN will then be ablated using standard techniques. If there are multiple branches of the GSN, each branch will be systematically identified and ablated.
| Study group | Role | What they receive |
|---|---|---|
| Surgical Resection Arm | Experimental | Surgical Resection of the Greater Splanchnic Nerve Receives: Procedure: Surgical Resection of the Greater Splanchnic Nerve |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blunting or delay in rise of Pulmonary Capillary Wedge Pressure (PWCP) or Pulmonary Artery Diastolic Pressure (PAD) during exercise
Measured: at 1 month post-procedure as compared to baseline
Secondary outcomes (1)
Reduction in resting Pulmonary Capillary Wedge Pressure (PWCP) or Pulmonary Artery Diastolic Pressure (PAD)
Measured: at 1 and 3 months post-procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2018
- Study start1 Aug 2016
- Primary completion30 Jun 2019
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Noblewell
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Coridea, Axon Therapies
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03715543
- Sponsor's protocol ID
- GSN FIH Study
- Status last verified
- Jun 2020
- First submitted
- 16 Aug 2018
- Last updated
- 30 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surgical Resection of the Greater Splanchnic Nerve in Subjects Having Heart Failure With Preserved Ejection Fraction: First-in-human Feasibility Trial
- ClinicalTrials.gov ID
- NCT03715543
- Acronym / sponsor ID
- GSN FIH Study
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- NoblewellIndustry (pharma, biotech, devices)
- Collaborators
- Coridea, Axon Therapies
- Study start
- 1 Aug 2016 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 23 Oct 2018 (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.
We believe that blocking of the Greater Splanchnic Nerve (GSN) will stop Sympathetic Nervous System (SNS) activity from reaching the splanchnic vessels and result in a redistribution of blood volume back into the splanchnic reservoir, which will result in reduction of central venous, pulmonary and right and left heart pressures. For patients having Heart Failure With Preserved Ejection Fraction (HFpEF) we expect these changes to improve dyspnea and capacity to exercise, improve quality of life, increased diuretic responsiveness, Furthermore, the expected benefits of unloading the central venous and arterial system through GSN ablation should improve hemodynamic control and lessen the incidence and severity of acute decompensations leading to reduced re-hospitalizations and associated healthcare costs. This has the potential for significant social and healthcare impact.
Detailed description
Heart failure (HF) is a major and growing public health problem with more than 5 million identified cases and an incidence of over 600,000 new cases per year in the United States alone. Close to 1 million hospitalizations for heart failure occur annually, accounting for over 6.5 million hospital days and a substantial portion of the estimated $37.2 billion that is spent each year on HF in the United States. Nearly half of all patients with HF have so called heart failure with preserved ejection fraction (HFpEF). The 5-year mortality for HFpEF has been reported as high as 50-65%. There are no current evidenced-based HFpEF therapies beyond diuretic control for fluid overload and standard treatments for comorbidities, making HFpEF an exemplary example of an unmet medical need of a rising societal burden and that is associated with substantial morbidity and mortality.
In HFpEF, sympathetic nervous system (SNS) hyperactivity results in decreased splanchnic capacitance causing more blood to be distributed into the central venous and arterial system. This leads to increase central venous pressure, pulmonary pressures and right/left heart pressures, which ultimately results in: congestions, diuretic resistance, acute decompensations leading to rehospitalization, dyspnea and intolerance to even mild exercise, and progressive diastolic dysfunction.
We believe that blocking of the GSN will stop SNS activity from reaching the splanchnic vessels and result in a redistribution of blood volume back into the splanchnic reservoir, which will result in reduction of central venous, pulmonary and right and left heart pressures. For patients with HFpEF we expect these changes to improve dyspnea and capacity to exercise, improve quality of life, increased diuretic responsiveness, Furthermore, the expected benefits of unloading the central venous and arterial system through GSN ablation should improve hemodynamic control and lessen the incidence and severity of acute decompensations leading to reduced re-hospitalizations and associated healthcare costs. This has the potential for significant social and healthcare impact.
Sympathetic and parasympathetic innervation is carried to the upper abdominal viscera by the GSN, lesser splanchnic nerve (LSN) and least splanchnic nerve (LTSN), which originate from the 5th to 8th, 9th to 10th, and 11th thoracic ganglia, respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Surgical Resection Arm | Experimental | Procedure: Surgical Resection of the Greater Splanchnic NerveSurgical Resection of the Greater Splanchnic Nerve |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients ≥ 18 years of age with guideline defined HFpEF class III/IV (EF>40% on optimal medical therapy)
- History of exertion-related dyspnea in last 3 months
- No evidence of clinically significant peripheral edema/fluid overload
- Resting PCWP or PAD > 15 mmHg or > 25 mmHg during exercise
- The ability understand and provide signed informed consent
Key exclusion criteria (17 listed)
- Myocardial infarction and/or percutaneous cardiac intervention within past 3 months; coronary artery bypass graft in past 3 months or current indication for coronary revascularization
- Admission for HF within the past month
- Systolic Blood Pressure (BP) < 120 mmHg or > 170 mmHg despite appropriate medical management
- Inability to perform Cardio Pulmonary Exercise Test (CPET)
- Presence of severe regurgitant or stenotic valve disease
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 |
|---|---|---|
| Surgical Resection of the Greater Splanchnic NerveVideo-Assisted Thoracoscopic Surgery (VATS) is performed under general anesthesia using existing, CE marked instrumentation. Two or more 5 mm incisions are used to pass a tiny video camera and a single dissecting instrument into the chest. These small ports are advantageous because the chance for infection and wound dehiscence are drastically reduced. This allows for a faster recovery by the patient and a greater chance for the wound to heal. In the procedure the GSN will be identified visually or through stimulation-induced hemodynamic reflex. The GSN will then be ablated using standard techniques. If there are multiple branches of the GSN, each branch will be systematically identified and ablated. | Procedure or surgery | Surgical Resection Arm |
Primary outcome
Blunting or delay in rise of Pulmonary Capillary Wedge Pressure (PWCP) or Pulmonary Artery Diastolic Pressure (PAD) during exercise
Time frame: at 1 month post-procedure as compared to baseline
1 secondary outcome
Reduction in resting Pulmonary Capillary Wedge Pressure (PWCP) or Pulmonary Artery Diastolic Pressure (PAD)
Time frame: at 1 and 3 months post-procedure
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2020.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Surgical Resection of the Greater Splanchnic Nerve in people with Heart Failure With Preserved Ejection Fraction, run by Noblewell at 2 sites in 2 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 5 inclusion and 17 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: finished, as of the sponsor's last update on 30 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Czechia, Poland. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Blunting or delay in rise of Pulmonary Capillary Wedge Pressure (PWCP) or Pulmonary Artery Diastolic Pressure (PAD) during exercise (time frame: at 1 month post-procedure as compared to baseline). 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 Jun 2020.