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A Pivotal Trial to Establish the Efficacy and Safety of Algisyl in Patients With Moderate to Severe Heart Failure (AUGMENT-HFII)

Primary Purpose

Heart Failure, Dilated Cardiomyopathy, Heart Failure With Reduced Ejection Fraction

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Algisyl
Standard Medical Therapy
Sponsored by
LoneStar Heart, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Algisyl, Heart Failure, Dilated Cardiomyopathy, Alginate Hydrogel, Heart Failure with Reduced Ejection Fraction, Congestive Heart Failure

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    Evidence-based therapy for heart failure is defined as an ACE-inhibitor (ACE-I), and/or angiotensin II receptor blockers (ARB) for patients at stable doses for 1 month prior to enrollment, if tolerated, and a beta blocker (carvedilol, metoprolol succinate, Nebivolol or bisoprolol) for 3 months prior to enrollment, if tolerated. Recent up-titration of the beta blocker is acceptable if the patient has been stable on this dose for 1 month prior to enrollment. Stable is defined as no more than a 100% increase or a 50% decrease in dose. Contraindications or intolerance to therapies should be documented. In those intolerant to both ACE-I and ARB, combination therapy with hydralazine and oral nitrate should be considered. Therapeutic equivalence for ACE-I substitutions is allowed within the enrollment stability timelines. Aldosterone inhibitor therapy should be added when NYHA Class III or IV symptoms occur on standard therapy. If aldosterone inhibitor therapy is to be administered in NYHA Class II patients, it must be initiated and optimized prior to enrollment. Eplerenone requires dosage stability for 1 month prior to enrollment. Diuretics should be used as necessary to keep the patient euvolemic. All heart failure therapeutics and dosages should be documented in the Case Report Forms.

  4. The patient must have cardiac resynchronization therapy (CRT) if clinically indicated, implanted ≥3 months prior to randomization.

    * Note: In those patients not receiving CRT or CRT-D therapy the investigator should not anticipate initiating this therapy within 6 months after randomization

  5. The patient must have an implanted cardio-defibrillator (ICD) if clinically indicated, implanted at least 30 days prior to randomization.

    *Note: If the patient has clinical indications for an ICD but refuses the ICD, this refusal of ICD therapy must be document in the medical record and the patient may be enrolled with this documentation.

  6. 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)
  7. The patients will have a left ventricular end diastolic dimension indexed to body surface area (LVEDDi) of greater than or equal to 30 mm/m2 (LVEDD/BSA) and an LVEDD of greater than or equal to 85 mm (measured within the last 30 days)
  8. Patients must have symptomatic heart failure with a Peak VO2 of 9.0 - 15.0 ml/min/kg (performed using a treadmill). 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 - 15.0 ml/min/kg from these two tests. All CPX tests performed for the study must have a Peak Respiratory Exchange Ratio (RER) of at least 1.0 to be accepted as a valid test.
  9. Patient's surgical risk must be considered reasonable and the evaluation of surgical risk should include review of coronary and left ventricular angiography. Surgical risk assessment should include the consideration of risk presented by prior surgical procedures such as prior mid-sternotomy surgical procedures.

    *Note: investigators should observe standard clinical practice for the management of antithrombotic therapy in patients undergoing surgical procedures in accordance with the American College of Chest Physicians Guidelines: Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th edition

  10. 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 presenting with a restrictive cardiomyopathy such as due to amyloidosis, sarcoidosis, or hemochromatosis
  4. Patient with a history of constrictive pericarditis
  5. Patients with a Q wave myocardial infarction (MI) within the last 30 days
  6. Patients with a recent history of stroke (within 60 days prior to the surgical procedure)
  7. A left ventricular (LV) wall thickness of the LV free-wall, at the mid-ventricular level, of less than 8 mm (screening echocardiography must confirm a minimum wall thickness of 8 mm)
  8. Patients with an estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2
  9. Clinically significant liver enzyme abnormalities, i.e., AST(SGOT) and ALT (SGPT) more than 2.5 times the upper limit of normal
  10. History of severe COPD (i.e., FEV 1< 1 liter or FEV1 < 50% predicted)
  11. 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
  12. 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Algisyl

    Standard Medical Therapy

    Arm Description

    Algisyl device (implants) administered during a surgical procedure.

    as per protocol

    Outcomes

    Primary Outcome Measures

    Peak VO2
    Change in Peak VO2 from baseline to 6 months of follow-up
    Primary Safety Endpoint: Death or Re-hospitalization for Worsening Heart Failure
    Death or Re-hospitalization for Worsening Heart Failure

    Secondary Outcome Measures

    NYHA Functional Class
    NYHA Functional Class
    Six-minute walk distance
    Six minute walk distance
    Peak VO2 at 12 months
    Change in Peak VO2 from baseline to 12 months of follow-up
    QOL
    Quality of Life as measured by KCCQ (Kansas City Cardiomyopathy Questionnaire)

    Full Information

    First Posted
    March 13, 2017
    Last Updated
    March 13, 2017
    Sponsor
    LoneStar Heart, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03082508
    Brief Title
    A Pivotal Trial to Establish the Efficacy and Safety of Algisyl in Patients With Moderate to Severe Heart Failure
    Acronym
    AUGMENT-HFII
    Official Title
    A Pivotal Trial to Establish the Efficacy and Safety of Algisyl in Patients With Moderate to Severe Heart Failure
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 2017 (Anticipated)
    Primary Completion Date
    January 2020 (Anticipated)
    Study Completion Date
    January 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    LoneStar Heart, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    Yes
    Device Product Not Approved or Cleared by U.S. FDA
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    AUGMENT-HF II is a study to evaluate the efficacy and safety of the Algisyl device. The purpose of this study is to investigate Algisyl employed as a method of left ventricular augmentation and restoration in patients with dilated cardiomyopathy. Algisyl will be injected into the myocardium under direct visualization during the surgical procedure. 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 dilation and heart failure. Because dilation, and not contractile dysfunction, appears to be responsible for the severity of the disease, the mitigation or prevention of the deleterious structural abnormalities of the left ventricle appears to be an important therapeutic target for patients with this life threatening illness. Hence, a therapy that specifically reduces LV wall stress, targets LV dilatation and LV remodeling may offer an important new alternative in the treatment of heart failure. Algisyl is being investigated based on evidence that suggests an ability of the implants to reduce wall stress, reshape the LV chamber and reduce the LV chamber size as well as prevent the progressive ventricular dilation and remodeling associated with HF. The physiologic response to progressive exercise using direct measures of ventilation and gas exchange via the cardiopulmonary exercise test is an important diagnostic tool in the management of the patient with HF, quantifying responses to therapy, and as a reliable prognostic utility for predicting outcomes in patients with HF. Numerous studies have established the strong association of peak VO2 with mortality and morbidity risk in HF. Peak VO2 conceptually is considered an overall global marker of cardiopulmonary health and is a reflection of the degree of impairment in ventricular function ( the heart's pumping capacity), oxygen delivery and oxygen utilization. Hence, employing the change in peak VO2 as a primary endpoint in this clinical study provides a strong objective measure that can be interpreted in independent blinded fashion, to evaluate the result of the therapeutic intervention and provide an equally strong assessment of the prognostic implications for patients in the study. This clinical evaluation is intended to provide confirmatory evidence of the effectiveness and safety of the device Algisyl in patients with advanced heart failure.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Heart Failure, Dilated Cardiomyopathy, Heart Failure With Reduced Ejection Fraction
    Keywords
    Algisyl, Heart Failure, Dilated Cardiomyopathy, Alginate Hydrogel, Heart Failure with Reduced Ejection Fraction, Congestive Heart Failure

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    240 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Algisyl
    Arm Type
    Experimental
    Arm Description
    Algisyl device (implants) administered during a surgical procedure.
    Arm Title
    Standard Medical Therapy
    Arm Type
    Active Comparator
    Arm Description
    as per protocol
    Intervention Type
    Device
    Intervention Name(s)
    Algisyl
    Other Intervention Name(s)
    intramyocardial injections of alginate hydrogel
    Intervention Description
    Algisyl device (implants) administered during a surgical procedure
    Intervention Type
    Drug
    Intervention Name(s)
    Standard Medical Therapy
    Other Intervention Name(s)
    Evidence based therapy for heart failure, heart failure medications, drug therapy
    Intervention Description
    as per protocol
    Primary Outcome Measure Information:
    Title
    Peak VO2
    Description
    Change in Peak VO2 from baseline to 6 months of follow-up
    Time Frame
    6 months
    Title
    Primary Safety Endpoint: Death or Re-hospitalization for Worsening Heart Failure
    Description
    Death or Re-hospitalization for Worsening Heart Failure
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    NYHA Functional Class
    Description
    NYHA Functional Class
    Time Frame
    6 months
    Title
    Six-minute walk distance
    Description
    Six minute walk distance
    Time Frame
    6 months
    Title
    Peak VO2 at 12 months
    Description
    Change in Peak VO2 from baseline to 12 months of follow-up
    Time Frame
    12 months
    Title
    QOL
    Description
    Quality of Life as measured by KCCQ (Kansas City Cardiomyopathy Questionnaire)
    Time Frame
    6 months
    Other Pre-specified Outcome Measures:
    Title
    MACE-free survival
    Description
    Major Adverse Cardiovascular Events (MACE)-free survival at 30 days, 6 months and 12 months
    Time Frame
    30 days, 6 months, 12 months
    Title
    MACE
    Description
    Occurrence of individual MACE components at 30 days, 6 months and 12 months
    Time Frame
    30 days, 6 months, 12 months
    Title
    MAE
    Description
    Major Adverse Events at 30 days, 6 months and 12 months
    Time Frame
    30 days, 6 months, 12 months
    Title
    Afib
    Description
    Overall incidence of atrial fibrillation and freedom from atrial fibrillation
    Time Frame
    30 days, 6 months, 12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    79 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: The patients must be able and willing to give written informed consent The patients will be adult (age ≥ 18 years and ≤ 79 years) males or females The patients must be on stable, evidence-based therapy for heart failure Evidence-based therapy for heart failure is defined as an ACE-inhibitor (ACE-I), and/or angiotensin II receptor blockers (ARB) for patients at stable doses for 1 month prior to enrollment, if tolerated, and a beta blocker (carvedilol, metoprolol succinate, Nebivolol or bisoprolol) for 3 months prior to enrollment, if tolerated. Recent up-titration of the beta blocker is acceptable if the patient has been stable on this dose for 1 month prior to enrollment. Stable is defined as no more than a 100% increase or a 50% decrease in dose. Contraindications or intolerance to therapies should be documented. In those intolerant to both ACE-I and ARB, combination therapy with hydralazine and oral nitrate should be considered. Therapeutic equivalence for ACE-I substitutions is allowed within the enrollment stability timelines. Aldosterone inhibitor therapy should be added when NYHA Class III or IV symptoms occur on standard therapy. If aldosterone inhibitor therapy is to be administered in NYHA Class II patients, it must be initiated and optimized prior to enrollment. Eplerenone requires dosage stability for 1 month prior to enrollment. Diuretics should be used as necessary to keep the patient euvolemic. All heart failure therapeutics and dosages should be documented in the Case Report Forms. The patient must have cardiac resynchronization therapy (CRT) if clinically indicated, implanted ≥3 months prior to randomization. * Note: In those patients not receiving CRT or CRT-D therapy the investigator should not anticipate initiating this therapy within 6 months after randomization The patient must have an implanted cardio-defibrillator (ICD) if clinically indicated, implanted at least 30 days prior to randomization. *Note: If the patient has clinical indications for an ICD but refuses the ICD, this refusal of ICD therapy must be document in the medical record and the patient may be enrolled with this documentation. 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) The patients will have a left ventricular end diastolic dimension indexed to body surface area (LVEDDi) of greater than or equal to 30 mm/m2 (LVEDD/BSA) and an LVEDD of greater than or equal to 85 mm (measured within the last 30 days) Patients must have symptomatic heart failure with a Peak VO2 of 9.0 - 15.0 ml/min/kg (performed using a treadmill). 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 - 15.0 ml/min/kg from these two tests. All CPX tests performed for the study must have a Peak Respiratory Exchange Ratio (RER) of at least 1.0 to be accepted as a valid test. Patient's surgical risk must be considered reasonable and the evaluation of surgical risk should include review of coronary and left ventricular angiography. Surgical risk assessment should include the consideration of risk presented by prior surgical procedures such as prior mid-sternotomy surgical procedures. *Note: investigators should observe standard clinical practice for the management of antithrombotic therapy in patients undergoing surgical procedures in accordance with the American College of Chest Physicians Guidelines: Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th edition 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: Patients for whom it is planned to receive CABG, MVR, heart transplantation or LVAD within the next 6 months. Patients presenting with cardiogenic shock. Patients presenting with a restrictive cardiomyopathy such as due to amyloidosis, sarcoidosis, or hemochromatosis Patient with a history of constrictive pericarditis Patients with a Q wave myocardial infarction (MI) within the last 30 days Patients with a recent history of stroke (within 60 days prior to the surgical procedure) A left ventricular (LV) wall thickness of the LV free-wall, at the mid-ventricular level, of less than 8 mm (screening echocardiography must confirm a minimum wall thickness of 8 mm) Patients with an estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 Clinically significant liver enzyme abnormalities, i.e., AST(SGOT) and ALT (SGPT) more than 2.5 times the upper limit of normal History of severe COPD (i.e., FEV 1< 1 liter or FEV1 < 50% predicted) 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 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Manoj Raghuraman
    Phone
    949-679-6185
    Ext
    101
    Email
    mraghuraman@Lshmail.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    A Pivotal Trial to Establish the Efficacy and Safety of Algisyl in Patients With Moderate to Severe Heart Failure

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