Clinical trial NCT02387112: Early Versus Emergency Left Ventricular Assist Device Implantation in Patients Awaiting Cardiac Transplantation
Official title: Early Versus Emergency Left Ventricular Assist Device Implantation in Patients Awaiting Cardiac Transplantation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: End Stage Heart Disease
Keywords: End stage heart disease
Ventricular assist device
Lead sponsor: German Heart Institute
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
name: Helmholtz Zentrum München
name: University Medicine Greifswald
name: University of Göttingen
First posted: 2015-03-12
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Event-free survival
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary outcomes:
measure: Stroke
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Listing for high-urgency (HU) cardiac transplantation
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: 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
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Number of patients with hospitalizations due to device failure
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Number of patients with adverse events due to device failure
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Number of device infections requiring antibiotics and/surgical intervention
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Number of patients with major bleedings (needing >4 Units of blood) following VAD implantation and major bleedings due to anticoagulation therapy
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Cardiovascular Death
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Number of patients suffering from secondary organ failure
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Maximum oxygen uptake (VO2 max)
timeFrame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Heart failure survival score
timeFrame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Seattle heart failure score
timeFrame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average)
measure: New York Heart Association class (NYHA)
timeFrame: Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Number of patients requiring urgent VAD implantation
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Rate of recurrent hospitalizations
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Number of patients receiving a donor heart
timeFrame: Randomisation untill transplantation (60 months at the most, 48 months on average)
measure: VAD explantation due to myocardial recovery
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Short Form-36 (SF-36)
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Minnesota Living with heart failure questionnaire (MLHFQ)
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Mini-mental state examination (MMSE)
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
measure: Quality-adjusted life year (QALY)
timeFrame: Randomisation untill month 60 (60 months at the most, 48 months on average)
Other outcomes:
Locations:
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg Bad Krozingen - Klinik für Herz- und Gefäßchirurgie
city: Bad Nauheim
country: Germany
facility: Kerckhoff Klinik Bad Nauheim
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW - Universitätsklinik der Ruhr-Universität Bochum
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin: Campus Benjamin Franklin
city: Berlin
country: Germany
facility: German Heart Center Berlin
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen - Herzchirurgische Klinik
city: Frankurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt - Klinik für Thorax-, Herz- und thorakale Gefäßchirurgie
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Med. Hochschule Hannover, Klinik für Herz-, Thorax-, Transplantations- und Gefäßchirurgie
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Herz- und Thoraxchirurgie
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig Holstein - Campus Kiel
city: Leipzig
country: Germany
facility: Heart Center Leipzig
city: Magdeburg
country: Germany
facility: Universitätsklinik für Herz- und Thoraxchirurgie
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg Klinik für Herz- und thorakale Gefäßchirurgie
city: München
country: Germany
facility: Herzchirurgische Klinik und Poliklinik des Klinikums der Universität München - Campus Großhadern
city: Münster
country: Germany
facility: Universitätskrankenhaus Münster
Study officials:
affiliation: German Heart Institute Berlin Germany
name: Volkmar Falk, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: