Early Versus Emergency Left Ventricular Assist Device Implantation in Patients Awaiting Cardiac Transplantation

End Stage Heart Disease Clinical Trial

Official title:

Early Versus Emergency Left Ventricular Assist Device Implantation in Patients Awaiting Cardiac Transplantation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02387112
• Other study ID #: DZHK VAD Study
• Secondary ID: VAD Study German
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 2015
• Est. completion date: December 2024

Study information

• Verified date: October 2023
• Source: German Heart Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: December 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Emergencies
• End Stage Heart Disease
• Heart Diseases

Intervention

Device:
• Early VAD implantation
Implantation of a left ventricular assist device

Locations

Country	Name	City	State
Germany	Universitäts-Herzzentrum Freiburg Bad Krozingen - Klinik für Herz- und Gefäßchirurgie	Bad Krozingen
Germany	Kerckhoff Klinik Bad Nauheim	Bad Nauheim
Germany	Herz- und Diabeteszentrum NRW - Universitätsklinik der Ruhr-Universität Bochum	Bad Oeynhausen
Germany	Charité - Universitätsmedizin Berlin: Campus Benjamin Franklin	Berlin
Germany	German Heart Center Berlin	Berlin
Germany	Universitätsklinikum Erlangen - Herzchirurgische Klinik	Erlangen
Germany	Universitätsklinikum Frankfurt - Klinik für Thorax-, Herz- und thorakale Gefäßchirurgie	Frankurt am Main
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Med. Hochschule Hannover, Klinik für Herz-, Thorax-, Transplantations- und Gefäßchirurgie	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Jena, Klinik für Herz- und Thoraxchirurgie	Jena
Germany	Universitätsklinikum Schleswig Holstein - Campus Kiel	Kiel
Germany	Heart Center Leipzig	Leipzig
Germany	Universitätsklinik für Herz- und Thoraxchirurgie	Magdeburg
Germany	Universitätsklinikum Gießen und Marburg Klinik für Herz- und thorakale Gefäßchirurgie	Marburg
Germany	Herzchirurgische Klinik und Poliklinik des Klinikums der Universität München - Campus Großhadern	München
Germany	Universitätskrankenhaus Münster	Münster

Sponsors (5)

Lead Sponsor	Collaborator
German Heart Institute	Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Helmholtz Zentrum München, University Medicine Greifswald, University of Göttingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival	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).	Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Stroke	Freedom from disabling and non-disabling strokes	Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Listing for high-urgency (HU) cardiac transplantation		Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	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		Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Number of patients with hospitalizations due to device failure		Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Number of patients with adverse events due to device failure		Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Number of device infections requiring antibiotics and/surgical intervention		Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Number of patients with major bleedings (needing >4 Units of blood) following VAD implantation and major bleedings due to anticoagulation therapy	Bleeding needing hospitalisation, blood transfusion and/or surgical interventions	Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Cardiovascular Death		Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Number of patients suffering from secondary organ failure	Time to event of renal and/or hepatic failure	Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Maximum oxygen uptake (VO2 max)		Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Heart failure survival score		Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Seattle heart failure score		Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	New York Heart Association class (NYHA)		Measured every 6 months from randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Number of patients requiring urgent VAD implantation		Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Rate of recurrent hospitalizations		Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Number of patients receiving a donor heart		Randomisation untill transplantation (60 months at the most, 48 months on average)
Secondary	VAD explantation due to myocardial recovery	Time to event	Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Short Form-36 (SF-36)	Quality of life questionnaire (QoL)	Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Minnesota Living with heart failure questionnaire (MLHFQ)	Quality of life questionnaire (QoL)	Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Mini-mental state examination (MMSE)	Quality of life questionnaire (QoL)	Randomisation untill month 60 (60 months at the most, 48 months on average)
Secondary	Quality-adjusted life year (QALY)		Randomisation untill month 60 (60 months at the most, 48 months on average)