The objective of the study is to assess the safety and performance of the Cardionomic cardiopulmonary nerve stimulation (CPNS) system in patients with acute decompensated heart failure. The intent of the study is descriptive in nature, without a…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
All analyses will be descriptive with no inferential statistical test.
1. Safety Measures through 6-months:
The following measures will be characterized in all enrolled subjects:
• Death
• Serious Adverse Events
• Procedure-related Adverse Events
• System-related Adverse Events
• Therapy-related Adverse Events
2. Performance Measures:
The following measures will be characterized in the Treatment Analysis Set:
• Characterize the change in pressures (e.g., RV dP/dt, RV, SBP, DBP, PA, etc)
and heart rate during Therapy OFF and Therapy ON start of therapy and daily
assessments
• Characterize the change in cardiac output (via the Fick method) from start of
therapy to end of therapy (only calculated in subset of subjects with an
arterial line and SpO2 may be used as a surrogate for SaO2)Characterize the
change in pressures through the therapy duration
• Characterize the change in mixed venous oxygenation saturation during Therapy
OFF and Therapy ON at start of therapy and daily assessments
• Characterize the change in mixed venous oxygenation saturation through the
therapy duration
• Characterize echocardiogram assessments during therapy OFF and therapy ON at
48 hours post baseline/randomization
The following measures will be characterized in the modified Intent-to-Treat
(mITT) set separately by the Lead-In Phase and the Randomized Phase:• Discharge
and follow-up oral medications:
• Medical treatment provided throughout hospitalization (e.g., medication
usage, mechanical support, etc)
• Change in NT-proBNP, serum creatinine, BUN and troponin throughout
hospitalization
• Change in dyspnea throughout hospitalization compared to enrollment
• Patient Global Assessment throughout hospitalization
• Change in KCCQ-12 from enrollment to 30-days post hospital discharge
• Hospital readmission rates within 30 days post hospital discharge
• Length of hospital stay
• Echocardiogram assessments at baseline and 48 hours post
baseline/randomization
• In-hospital mortality
Secondary outcome
Not applicable, all study parameters are described in section above
Background summary
Heart failure affects an estimated 26 million people worldwide, resulting in
more than 1 million hospital admissions each year in both the United States and
Europe. Heart failure is a progressive and complex condition that results from
the reduced contractility of the heart. Patients who enroll may experience the
following symptoms: shortness of breath, tiredness and weakness, swelling in
the legs, ankles and feet, or fast and irregular heartbeat
Current treatments for acute decompensated heart failure have remained
unchanged for many years and consist mainly of administering drugs to relieve
symptoms.
Previous research has shown that stimulation of the cardiopulmonary nerve by
the CPNS system can increase the contractility of the heart without increasing
the heart rate. The aim of this study is to further investigate the safety and
operation of the CPNS system.
Study objective
The objective of the study is to assess the safety and performance of the
Cardionomic cardiopulmonary nerve stimulation (CPNS) system in patients with
acute decompensated heart failure. The intent of the study is descriptive in
nature, without a formal hypothesis testing.
Study design
The CPNS Pilot Study is a prospective, two-phased, multi-center and
multinational study.
The study is designed with two phases: the Lead-In Phase and the Randomized
Phase.
The purpose of the Lead-In Phase is to gain first experience with the CPNS
System in ADHF patients. Up to 30 subjects will be enrolled to refine study
methods and develop practical experience.
The Randomized Phase will follow and includes up to 60 subjects 2:1 randomized
to characterize outcome differences between treatment and control groups.
All patients will be followed through 6 months post discharge.
Intervention
Patients in phase 1 or patients in phase 2 who are randomised to the CPNS
treatment receive the CPNS system implanted:
The CPNS System is a neuromodulation system used to treat ADHF, the sudden or
slow deterioration of chronic heart failure. The CPNS System is intended to
provide acute (<= 5 days) endovascular stimulation of the cardiac autonomic
nerves in the right pulmonary artery in hospitalized ADHF patients.
The system consists of an acute transient neuromodulation pacing catheter (CN2
catheter) placed into the right pulmonary artery through venous access and a
modified external stimulator. Through electrical stimulation of the terminal
sympathetic nerve branches in the cardiopulmonary plexus, this can provide an
inotropic and / or lusitropic therapeutic effect.
The procedure to place the catheter takes place in the cath lab and takes
approximately 2 to 3 hours, including the testing to test correct placement.
The system will be removed during a +/- 1 hour intervention after a maximum
treatment of 5 days.
Detailed description of the implant and explant procedures can be found in the
study protocol and the instructions for use.
Patients randomized to the control arm in phase 2 receive standard treatment
for their heart failure (standard of care) without a CPNS system.
Study burden and risks
There are risks associated with performing the CPNS catheter implantation, the
use of anesthesia, and the CPNS therapy itself. The risks associated with the
implantation procedure of a CPNS catheter are comparable to those of a standard
cardiac catheterization procedure. These risks are listed below. In addition,
the CPNS treatment can also have side effects that we do not yet know.
• Allergic reaction to the catheters, dye or medications used during or after
the procedure
• Bleeding that may require blood transfusion
• Complications related to the fluid used to view your vessels under x-ray
during the procedure (contrast agent)
• Complications at catheter insertion site (i.e., bruising, pooling of blood
(hematoma), infection, numbness, bleeding)
• Nausea and/or vomiting
• Confusion or decreased awareness of surrounding environment (delirium)
• Bruising, blood clots or blood collection
• Collapsed lung
• Damage to blood cells, blood vessels, nerves, or the heart
• Damage to or narrowing of the heart valves
• Death
• Fluid or inflammation around the heart or lungs
• Electrical shock and/or burn
• Heart attack
• High or low blood pressure
• Immune response to device components
• Infection
• Internal bleeding
• Irregular or stopped heartbeat that may or may not require an electrical shock
• Kidney damage
• Obstruction of blood flow in the arteries or heart
• Pain or discomfort - during or after the procedure that may require treatment
with pain medications
• Surgical intervention for device malfunction or removal
• Swelling or distension
There are additional risks that could possibly be associated with the test
procedures performed for the clinical study. These potential risks are
described below:
• There are risks related to the blood tests required for the study (e.g.,
excessive bleeding, fainting or light-headedness, pooling of blood (hematoma),
infection, or requirement of multiple punctures to locate a vein to draw the
sample).
• This study involves a small amount of radiation during the procedure
angiograms. Radiation may slightly elevate the risk for cancer.
The full list of risks associated with general anesthesia, the procedure and
treatment as well as the risk mitigation process is described in the study
protocol (section 9).
Campus Drive 601 (Suite 12)
New Brighton, MN 55112
NL
Campus Drive 601 (Suite 12)
New Brighton, MN 55112
NL
Listed location countries
Age
Inclusion criteria
Subjects must meet all the following inclusion criteria to be eligible to
participate in this study:
1. At least 18 years of age, or older if required by local law
2. Admitted to the hospital with a principal diagnosis of acute decompensated
heart failure.
3. BMI adjusted BNP >= 500 pg/mL or NT-pro-BNP >= 2000 pg/mL; 4% reduction in
BNP/NT-proBNP for every increase of 1 kg/m2 in BMI above a reference of 20kg/m2
(Refer to Appendix B: BNP/NT-proBNP corrected for BMI)
4. Left ventricular ejection fraction <= 45%; documented within previous 12
months
5. At least one sign or symptom of fluid overload
6. At least one of the following:
o Persistent inadequate diuretic response
o At least one sign or symptom of low perfusion
Exclusion criteria
1. First IV treatment upon presentation in hospital to randomization is > 48
hours
2. Received an inotrope during current hospitalization or anticipated to
receive an inotrope in the 12 hours following enrollment
3. Requires mechanical support (e.g., mechanical circulatory support,
ultrafiltration) or anticipated to receive mechanical support in the 12 hours
following enrollment
4. Manually measured systolic blood pressure < 80 mmHg at screening
5. Manually measured systolic blood pressure > 130 mmHg at screening
6. Symptomatic hypotension
7. eGFR < 25 mL/min/1.73m2
8. Has an active infection
9. Has an active or passive implantable device that may interfere with CPNS
therapy per physician discretion
10. Has a cardiac resynchronization therapy (CRT) device or a pacemaker
11. Has an implantable cardioverter defibrillator (ICD) and is pacemaker
dependent or has had a sustained VT/VF episode in the previous 90 days (a
subject can be enrolled if he/she meets this criterion, the physician deems it
appropriate to suspend therapies during hospitalization and leads have been
implanted for at least six months prior to the study procedure) 12. Permanent
or persistent atrial fibrillation with uncontrolled ventricular response
(ventricular rate > 125 BPM) at time of enrollment
13. Unstable angina or documented myocardial infarction within last 30 days
14. Prior heart transplant
15. History of severe mitral or aortic stenosis or regurgitation
16. History of pulmonary embolism within the last 6 months
17. History of hyper-coagulation disorders
18. History of more than one CABG procedure
19. History of severe pulmonary hypertension (pulmonary arterial systolic
pressure >= 75 mmHg)
20. Diagnosis of primary pulmonary hypertension
21. Diagnosis of congenital heart disease
22. Participating in concurrent trial unless approved by Cardionomic study
manager
23. Pregnant or childbearing age and not on reliable form of birth control
24. Allergy to nickel, fentanyl, midazolam, propofol, heparin, eggs, egg
products, soybeans or soy products
25. Unwilling or unable to provide consent
26. Exclusion criteria by local law (e.g., age, prisoner, etc)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04814134 |
| CCMO | NL75779.000.21 |