The objective of the AUGMENT-HF study is to provide evidence for the safety profile associated with the Algisyl-LVR* device and initial evidence for the efficacy of the device.
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. The primary safety outcome is to estimate the 30 day mortality associated
with the implantation of the Algisyl-LVR device;
2. The primary efficacy outcome is the change in Peak VO2 from baseline to 6
months of follow-up.
Secondary outcome
1. Incidence of major surgical complications (30 days post op);
2. Incidence of major anesthesia-related complications;
3. Incidence of major adverse cardiac event (MACE). MACE is defined as cardiac
death, cardiac arrest, myocardial infarction, sustained ventricular
arrhythmias, pulmonary edema, acute heart failure, unstable angina and major
bleeding (6 months);
4. Overall incidence and freedom from serious adverse events (6 months);
5. All-cause mortality and cardiovascular mortality (6 months);
6. All-cause hospitalizations and heart failure hospitalizations (6 months);
7. Time to first heart failure hospitalization (6 months);
8. Number of days alive out of hospital (all cause) during the 1st 6 months;
9. Laboratory assessments (6 months);
10. Adverse events;
11. Cardiac imaging (Echo and MRI or Nuclear Imaging) measures of changes in
left ventricular volume, ejection fraction, dimensions, and mitral
regurgitation (6 months);
12. Six-minute walk distance (6 months);
13. Quality of life as measured by KCCQ (6 months);
14. Patient Global Assessment (PGA) (6 months);
15. NYHA Functional Class (6 months).
Background summary
Heart Failure (HF) results in poor life expectancy, impaired quality of life,
repeated hospitalisations and is a considerable economic burden, accounting for
1-2% of health care expenditure in European countries. The incidence of HF
approaches 10 per 1000 population after 65 years of age, and approximately 80%
of patients hospitalised with HF are older than 65 years. Despite current drug
and device therapies for the treatment of HF, its prognosis remains poor. In
addition, the treatment choices for patients with advanced HF are limited and
include for the most part heart transplantation, left ventricular assist
devices, or biventricular pacing. However, these therapeutic solutions are not
an option for all HF patients because of either clinical contraindications or
economical considerations.
Structural abnormalities in the heart are known to play a central role in HF,
and clinical evidence supports a strong causal relationship between cardiac
chamber dilatation and HF. Because dilation, and not contractile dysfunction,
appears to be responsible for the severity of the disease, the mitigation or
prevention of the deleterious dilation process appears to be an important
therapeutic target for patients with this diagnosis. Hence, a therapy that
specifically targets progressive Left Ventricular (LV) dilatation and
remodeling by thickening the LV wall, reducing wall stress and reducing the LV
chamber size may offer an important new alternative in the treatment of HF.
The medical device under investigation in this study is called Algisyl-LVR*.
This is a novel medical device and procedure intended to prevent or reverse the
progression of LV remodeling in dilated cardiomyopathy. Alginate is a
polysaccharide hydrocolloid found as a structural component in marine brown
algae. The product is highly biocompatible (cytotoxicity, mutagenicity,
hemolysis, irritation or sensitization) and the kinetics of the alginate have
been tuned such that Algisyl-LVR is similar in functional properties to
myocardial tissue; a spongy, compliant material. Two different alginate
components form a calcium cross-linked hydrogel minutes after mixing, thus is
readily injectable. Alginate polymers do not biochemically degrade in higher
organism tissues.
The tissue engineering principles employed with Algisyl-LVR target the most
critically important aspect of the failing ventricle by directly reducing wall
stress (improving myocyte performance) and strategic, targeted reduction of the
inner chamber radius. This approach is unique and avoids the potentially
unintended negative consequences of other therapies such as altering diastolic
performance, peripheral hemodynamics or increasing myocyte workload.
Algisyl-LVR is implanted (injected) directly into the myocardial tissue during
a single surgical (cardio-thoracic) procedure. The implants are intended to be
permanent and serve to increase LV wall thickness, reduce LV wall stress and
result in a reduced LV chamber size with an improved pumping efficiency. The
placements of the implants also serve as a prosthetic scaffold that prevents
ongoing ventricular enlargement and restore a more beneficial shape to a
dilated left ventricle. Experimental data demonstrates that the device
produces an immediate and sustained improvement in cardiac function.
The intended clinical benefits of Algisyl-LVR are to improve the failing
heart*s structure and function with an associated improvement in the patient*s
clinical status and quality of life.
For further information, see study protocol (version 1.1. dated June 20th 2011)
page 13, introduction and page 19, study rationale.
Study objective
The objective of the AUGMENT-HF study is to provide evidence for the safety
profile associated with the Algisyl-LVR* device and initial evidence for the
efficacy of the device.
Study design
AUGMENT-HF is a prospective, controlled, randomized, multi-centre trial with
two parallel groups of equal size. Eligible patients will be randomized
(randomization will be concealed) to either the Investigational Device Group or
to the Usual Care group. The moment of randomization will be the starting point
of follow-up and the starting point of follow-up for surgical mortality and
surgical complications will be as of the date when the cardio-thoracic
procedure is performed (or attempted). The primary safety outcome is 30 day
all-cause mortality associated with the implantation of the Algisyl-LVR device.
The primary efficacy outcome is change in Peak VO2 from baseline to 6 months of
follow-up. The secondary outcomes will evaluate the effects of the device,
relative to the control group through functional, structural, biochemical and
electrocardiographic evaluations performed at 3, 6 and 12 months following
randomization. Patient safety will be overseen by an Independent Data Safety
Monitoring Board. Study outcomes will be adjudicated by a Clinical Endpoint
Committee (CEC) blinded to study group allocation. The cardiopulmonary exercise
data, cardiac imaging, blood tests and 24-hr Holter Monitor data will be
evaluated by central core laboratories, all blinded to study group allocation.
Patients assigned to the Aligysl-LVR group will have the Algisyl-LVR* device
(implant) administered during a surgical procedure which will be scheduled
between 7 to 10 days after randomization.
Patients randomly assigned to control group will be treated for their heart
failure in accordance with the current recommendations. After having completed
the 12-month follow-up visits, patients assigned to the control group will be
provided the option of enrolling in Clinical Study LSH-11-001: An Open Label
Rollover Trial for Patients Randomized to the Control Group of Study
LSH-10-001. Patients must meet the inclusion and exclusion criteria as stated
in Study LSH-10-001 to be eligible for Study LSH-11-001 and to receive the
Algisyl-LVR* device.
The follow-up in this study is divided into two phases - the *efficacy* phase
and *extended follow-up phase*. The efficacy phase will end after the last
randomized patient has completed the 6 month visit. During this time, all
patients will be contacted by telephone 30 days after randomization and will be
seen at the out-patient clinic at 3 and 6 months after randomization to undergo
repeat testing of functional and cardiac structural parameters in addition to a
Quality of Life Assessment. The primary efficacy and secondary safety and
efficacy outcomes will be analyzed at this time-point. During the *extended
follow-up* phase, patients will return to the out-patient clinic every 6 months
until each patient has completed, in total, 24 months of follow-up. During this
phase, data collection will be focused on long-term safety.
Intervention
Patients randomized to the Investigational Device group will be admitted to the
hospital within 7 and 10 days after randomization to undergo the
cardio-thoracic surgical procedure employing a limited anterolateral
thoracotomy (approximately 10 to 15 cm) to implant Algisyl-LVR. It is expected
that the surgery will last maximally 1 hour. To ensure patient safety, standard
intraoperative monitoring tools will be utilized which will include continuous
cardiac monitoring, arterial pressure lines, transesophageal echocardiography,
and pulmonary artery pressure measurements. The surgeon will administer the
Algisyl-LVR device as described in the Algisyl-LVR Instructions for Use Manual.
The Cardiac surgeons will undergo adequate, documented training prior to
implanting the device. In addition, the surgeon will be proctored by a cardiac
surgeon who has previously implanted the Algisyl-LVR device. It is expected
that patients will remain in hospital up to maximally 8 days following the
procedure.
Study burden and risks
1. Burden and risks:
The nature and extent of the risks and benefits associated with participation
in the AUGMENT-HF study is detailed in section 14 of the trial protocol
(version 1.1, dated June 20th 2011). In addition, all identified known risks
are described in the Algisyl-LVR Investigator Brochure (version 5.1, dated
August 09th 2011).
Risks associated with the cardio-thoracic surgery:
Patient risks or discomforts may be expected to include any of the standard
risks of a patient undergoing cardiothoracic surgery.
Risks associated with the investigational device:
Possible risks due to the investigational device may include arrhythmias from
heart manipulation during device placement. Thrombo-emboli resulting from
either dislodgment of any intracardiac thrombus or inadvertent penetration of
the device (hydrogel) into the LV cavity during device placement could result
in stroke, pulmonary embolism, myocardial infarction, or peripheral embolism.
Like all implanted devices, this investigational device may increase the risk
of infection. Hemodynamic compromise could result from an improper use of the
device, from damage to coronary arteries or abrasion of the heart surface
during device placement. However, animal studies have evaluated the effects on
cardiac tissue and have found no evidence of problems when the device is
implanted. Animal testing has also demonstrated that the device implant is
biocompatible.
Evaluation of the occurrence of events such as excessive fibrosis or
constrictive disease related to the investigational device will be monitored
throughout the duration of the study. No such events have been observed to date
in either animal or human studies. If the physician determines that cardiac
compression or damage related to device placement, subsequent fibrosis
formation, or tissue response is resulting in hemodynamic compromise not
treatable by cardiac medication alone, the following surgical options are
available:
• Superficial grid-like scoring of the epicardial surface to release
constriction. The medical literature contains reports of several successful
applications of this technique in patients with constrictive pericarditis
associated with constrictive epicarditis. See: Heimbecker R, et al., Surgical
Technique for the Management of Constrictive Epicarditis Complicating
Constrictive Pericarditis (The Waffle Procedure), Annals of Thoracic Surgery,
Vol 36, No 3, Nov 1983. See also: Faggian G, et al., Constrictive Epicarditis
After Open Heart Surgery: The Turtle Cage Operation, Journal of Cardiac
Surgery, Vol 5, No 4, 1990;
• Placement of cardiac assist or replacement device (unless the patient has
contraindications);
• Cardiac transplant (unless the patient is contraindicated for transplant).
The risks for participation in this study have been minimized by:
• Selection of experienced clinical sites;
• Adequate and documented training of the cardio-thoracic surgeon. In addition,
the surgeons will be proctored for the first two patient cases;
• Adequate training of the other members of the site team that will be
responsible for the follow-up of the patients during the study.
• A rigorous patient selection (i.e. strict inclusion and exclusion criteria
defined in the study protocol);
• A Data Safety Monitoring Board (DSMB) will be responsible to oversee patient
safety. The committee will review the patient data at pre-specified time points
during the conduct of the study;
• Clear and unambiguous stopping rules have been defined in the study protocol
(see section 4.1, page 21 of the study protocol, version 1.1, dated June 20th
2011). The DSMB will be responsible to implement the stopping rules;
• Frequent monitoring: Frequent on-site monitoring visits will be performed to
ensure proper conduct and management of the study.
2. Potential Benefits
The benefits to patients participating in this study will include the
recognition that they are contributing to a better understanding of the
potential use of the Algisyl-LVR device. Patients may benefit from closer
monitoring of their health. Patients allocated to the Algisyl-LVR group may
show improvement in clinical signs and symptoms related to their cardiac
disease in addition to an improvement in Health-Related Quality of Life.
LONESTAR HEART, INC 26051 MERIT CIRCLE, SUITE 102
LAGUNA HILLS, CA 92653
US
LONESTAR HEART, INC 26051 MERIT CIRCLE, SUITE 102
LAGUNA HILLS, CA 92653
US
Listed location countries
Age
Inclusion criteria
1. The patients must be able and willing to give written informed consent;
2. The patients will be adult (age >= 18 years and <= 79 years) males or females;
3. The patients must be on stable, evidence-based therapy for heart failure;
4. The patients will have a left ventricular ejection fraction equal to or less than 35% via echocardiography, cardiac catheterization, radionuclide scan, or magnetic resonance imaging (measured within the last 30 days);
5. The patients will have a left ventricular end diastolic dimension indexed to body surface area (LVEDDi) of 30 to 40mm/m2 (LVEDD/BSA) (measured within the last 30 days);
6. Patients must have symptomatic heart failure with a Peak VO2 of 9.0 - 14.5 ml/min/kg (performed using a bicycle ergometer). Patients must perform two CPX tests (within 30 days of randomization and performed at least 20 hours apart) that differ by no more than 15% in the observed value for Peak VO2 and have a mean value of 9.0 - 14.5 ml/min/kg from these two tests;
7. Patient*s surgical risk must be considered reasonable and the evaluation of surgical risk should include review of coronary and left ventricular angiography;
8. If female, the patients must be (a) post-menopausal, (b) surgically sterile, or (c) using adequate birth control and have a negative serum pregnancy test within 7 days prior to administration of study device.
Exclusion criteria
1. Patients for whom it is planned to receive CABG, MVR, heart transplantation or LVAD within the next 6 months;
2. Patients presenting with cardiogenic shock;
3. Patients who have undergone a previous mid-sternotomy surgical procedure are excluded unless the surgeon*s assessment is that the left sided limited thoracotomy is feasible and considered reasonable surgical risk;
4. Patients presenting with a restrictive cardiomyopathy such as due to amyloidosis, sarcoidosis, or hemochromatosis;
5. Patient with a history of constrictive pericarditis;
6. Patients with a Q wave myocardial infarction (MI) within the last 30 days;
7. Patients with a recent history of stroke (within 60 days prior to the surgical procedure);
8. A left ventricular (LV) wall thickness of the LV free-wall, at the midventricular level, of less than 8 mm (screening echocardiography must confirm a minimum wall thickness of 8 mm);
9. Patients with a serum creatinine > 2.5 mg/dL;
10. Clinically significant liver enzyme abnormalities, i.e., AST(SGOT) and ALT (SGPT) more than 2.5 times the upper limit of normal;
11. History of severe COPD (i.e., FEV 1< 1 liter or FEV1 < 50% predicted);
12. The patients will not be receiving concurrently an investigational Product in another clinical trial or have received an investigational Product in another clinical trial in the 30 days prior to enrollment;
13. A life expectancy of less than 1 year or any other condition that, in the opinion of the clinical investigator, might compromise any aspect of the trial.
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 |
|---|---|
| CCMO | NL37005.100.12 |