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Trial record 1 of 1 for:    NCT 02387112
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Early Versus Emergency Left Ventricular Assist Device Implantation in Patients Awaiting Cardiac Transplantation

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ClinicalTrials.gov Identifier: NCT02387112
Recruitment Status : Recruiting
First Posted : March 12, 2015
Last Update Posted : November 6, 2019
Sponsor:
Collaborators:
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
Helmholtz Zentrum München
University Medicine Greifswald
University of Göttingen
Information provided by (Responsible Party):
German Heart Institute

Tracking Information
First Submitted Date  ICMJE June 24, 2013
First Posted Date  ICMJE March 12, 2015
Last Update Posted Date November 6, 2019
Study Start Date  ICMJE July 2015
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2019)
Event-free survival [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
The time to the composite end-point of all-cause death, high urgent cardiac transplantation, disabling stroke , HF hospitalizations (including emergency room HF visits >6 hrs).
Original Primary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
Mortality [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
Mortality in both groups between listing for cardiac transplantation in T Status and follow-up (5 years at the most, 4 years on average)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2019)
  • Stroke [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Freedom from disabling and non-disabling strokes
  • Listing for high-urgency (HU) cardiac transplantation [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients with de novo right heart failure measured by decreasing right heart ejection fraction, increasing central venous pressure and/or secondary organ failure needing catecholamines and/or right ventricular circulatory support [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients with hospitalizations due to device failure [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients with adverse events due to device failure [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of device infections requiring antibiotics and/surgical intervention [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients with major bleedings (needing >4 Units of blood) following VAD implantation and major bleedings due to anticoagulation therapy [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Bleeding needing hospitalisation, blood transfusion and/or surgical interventions
  • Cardiovascular Death [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients suffering from secondary organ failure [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Time to event of renal and/or hepatic failure
  • Maximum oxygen uptake (VO2 max) [ Time Frame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Heart failure survival score [ Time Frame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Seattle heart failure score [ Time Frame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • New York Heart Association class (NYHA) [ Time Frame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients requiring urgent VAD implantation [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Rate of recurrent hospitalizations [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients receiving a donor heart [ Time Frame: Randomisation untill transplantation (60 months at the most, 48 months on average) ]
  • VAD explantation due to myocardial recovery [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Time to event
  • Short Form-36 (SF-36) [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Quality of life questionnaire (QoL)
  • Minnesota Living with heart failure questionnaire (MLHFQ) [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Quality of life questionnaire (QoL)
  • Mini-mental state examination (MMSE) [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Quality of life questionnaire (QoL)
  • Quality-adjusted life year (QALY) [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
  • Stroke [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Freedom from disabling and non-disabling strokes
  • Listing for high-urgency (HU) cardiac transplantation [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients with de novo right heart failure measured by decreasing right heart ejection fraction, increasing central venous pressure and/or secondary organ failure needing catecholamines and/or right ventricular circulatory support [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients with adverse events due to device failure [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of device infections requiring antibiotics and/surgical intervention [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Cardiovascular Death [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients suffering from secondary organ failure [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Time to event of renal and/or hepatic failure
  • Short Form-36 (SF-36) [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Quality of life questionnaire (QoL)
  • Minnesota Living with heart failure questionnaire (MLHFQ) [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Quality of life questionnaire (QoL)
  • Mini-mental state examination (MMSE) [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Quality of life questionnaire (QoL)
  • Number of patients receiving a donor heart [ Time Frame: Randomisation untill transplantation (60 months at the most, 48 months on average) ]
  • Maximum oxygen uptake (VO2 max) [ Time Frame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Heart failure survival score [ Time Frame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Seattle heart failure score [ Time Frame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • Number of patients with major bleedings (needing >4 Units of blood) following VAD implantation and major bleedings due to anticoagulation therapy [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Bleeding needing hospitalisation, blood transfusion and/or surgical interventions
  • New York Heart Association class (NYHA) [ Time Frame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • VAD explantation due to myocardial recovery [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
    Time to event
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: March 6, 2015)
  • Quality-adjusted life year (QALY) [ Time Frame: Randomisation untill month 60 (60 months at the most, 48 months on average) ]
  • 6 minutes walking test [ Time Frame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average) ]
 
Descriptive Information
Brief Title  ICMJE Early Versus Emergency Left Ventricular Assist Device Implantation in Patients Awaiting Cardiac Transplantation
Official Title  ICMJE Early Versus Emergency Left Ventricular Assist Device Implantation in Patients Awaiting Cardiac Transplantation
Brief Summary The aim of the study is to assess whether, in patients who are listed for cardiac transplantation in transplantable (T) status, early implantation of a left ventricular assist device is superior to the current therapeutic strategy of medical heart failure therapy and assist device implantation only after serious deterioration of the patient's condition.
Detailed Description

Heart transplantation is considered the gold-standard therapy for end-stage systolic heart failure but the shortage of donor hearts in Germany and other countries has led to widespread use of left ventricular assist devices (LVAD). Even on the transplant list, patients' condition often deteriorate due to worsening heart failure so that they need an LVAD as a bridge until transplantation. The high mortality (one in five patients on the waiting list dies within 1 year) reflects the severity of the disease. In comparison, technical progress has reduced the complication rate seen with assist devices and, according to recent data, mortality during LVAD support is low. Patient status prior to LVAD implantation is a strong indicator for postoperative outcome, i.e. patients in worse condition are more likely to develop complications. Thus, the comparison between the standard indication and early LVAD implantation (T-status) appears timely and clinically necessary.

The paucity of donor hearts necessitates the prospective evaluation of alternative treatment regimens. The aim of the study is to assess whether, in patients with end-stage heart failure awaiting cardiac transplantation, a strategy involving early LVAD implantation is superior to a strategy of conservative medical heart failure therapy and assist device implantation only after severe deterioration of heart failure.

The investigators expect to gain insights that will be trail-blazing for the future treatment of patients with heart failure on the transplantation waiting list, including aspects of their medical care. If the study hypotheses are confirmed, the treatment of these seriously ill patients could be, on the one hand, further optimized. On the other hand, positive economic effects are highly probable.

The results will form the basis of future guidelines for the treatment of this group of patients.

Thus the study will also make a contribution to solving the problem of the ever increasing number of patients on the waiting list as opposed to the decreasing willingness to donate organs for transplantation.

As a mean of quality control of the conducted study and to retrieve more data in this population all patients who fulfill the eligibility criteria of the study but do not consent to randomization are included in a standard treatment registry.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE End Stage Heart Disease
Intervention  ICMJE Device: Early VAD implantation
Implantation of a left ventricular assist device
Study Arms  ICMJE
  • Experimental: Early VAD implantation
    The experimental intervention is early implantation of a left ventricular assist device (early VAD). Patients randomized to early VAD implantation will obtain a VAD within 28 days after randomization.
    Intervention: Device: Early VAD implantation
  • No Intervention: Emergency VAD implantation
    The control intervention is conservative heart failure treatment, with LVAD implantation in the case of worsening heart failure (emergency VAD). All patients randomized to the control intervention will be treated according to standard medical practice. In brief, these patients are closely monitored (scheduled regular visits to outpatient department depending on the patient's condition and at least every 6 months). If the condition worsens the patient may qualify for high urgency (HU) listing and/or for VAD implantation.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 10, 2019)
200
Original Estimated Enrollment  ICMJE
 (submitted: March 6, 2015)
500
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Patient (male or female) eligible for heart transplantation and accepted in T Status (transplantable) on the waiting list
  • Age 18 to 65 years
  • Signed informed consent
  • >30% 1-year mortality with the Seattle Heart Failure Model (SHFM) or at least three of the following criteria (a) to (f):

    1. cardiac index (CI) <2.5 l/min/m²
    2. pulmonary capillary wedge pressure >15 mmHg
    3. maximal oxygen uptake (VO2max) ≤10.0 ml/kg/min or ≤12.0 ml/kg/min in patients intolerant of a ß-blocker
    4. ratio of minute ventilation (VE) to carbon dioxide (VCO2) production (VE/VCO2) slope of >35
    5. at least two hospitalizations for heart failure within the previous 12 months
    6. documented increase of brain natriuretic peptide (BNP) or NTproBNP levels despite optimal medical therapy

Exclusion Criteria

  • Listing for transplantation of other organs in addition to heart
  • Previous cardiac surgeries (other than pacemaker or ICD surgeries)
  • Contraindications to assist device implantation (e.g. mechanical aortic valve, aortic insufficiency)
  • Contraindications to anticoagulation
  • Expected need for a right ventricular assist device/biventricular support expected (e.g. due to tricuspid valve insufficiency grade 3+, right ventricular ratio short/long axis ≥0.6, ratio of right to left ventricular end-diastolic diameter (RVEDD/LVEDD) >0.72, restrictive cardiomyopathy)
  • Presence of catecholamine support or intra-aortic balloon counterpulsation (IABP)
  • Overt infections
  • Fixed pulmonary hypertension (i.e. pulmonary arterial pressure (PAP) >60 mmHg and mean transpulmonary gradient (TPG) >15 mmHg or pulmonary vascular resistance (PVR) >6 Wood units despite optimal medical treatment)
  • Renal insufficiency (glomerular filtration rate (GFR) <30ml/min or need for hemodialysis or hemofiltration)
  • Significant coagulopathies
  • Systemic lupus erythematosus, sarcoid, or amyloidosis that has multisystem involvement and is still active
  • Drug abuse and/or alcohol abuse
  • Incompliance
  • Elevated panel reactivity levels of >50 %
  • Pregnancy or breast feeding in women
  • Participation in other investigational trials
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christoph Knosalla, MD, PhD ++49 30 4593 ext 2000 knosalla@dhzb.de
Contact: Sabine Hübler, MD, MBA ++49 30 4593 ext 2201 shuebler@dhzb.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02387112
Other Study ID Numbers  ICMJE DZHK VAD Study
VAD Study Germany ( Other Grant/Funding Number: DZHK/BMBF Germany )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party German Heart Institute
Study Sponsor  ICMJE German Heart Institute
Collaborators  ICMJE
  • Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
  • Helmholtz Zentrum München
  • University Medicine Greifswald
  • University of Göttingen
Investigators  ICMJE
Principal Investigator: Volkmar Falk, MD, PhD German Heart Institute Berlin Germany
PRS Account German Heart Institute
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP