Clinical trial NCT01879670: Partial Left Ventricular Support in Advanced Heart Failure
Official title: Partial Left Ventricular Support in Advanced Heart Failure
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Heart Failure
Heart-Assist Devices
Lead sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Universitaire Ziekenhuizen KU Leuven
First posted: 2013-06-18
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients will be selected from advanced heart failure clinics at two tertiary heart hospitals with large cardiac transplantation and mechanical circulatory support programmes.

Brief summary: Heart failure is a common condition, and the number of people with advanced disease continues to increase. We need new treatments that improve patients' symptoms and extend life. Recently the new CircuLite Synergy pump has come into use. It is the smallest pump manufactured to date and does not cover the full work of the heart, instead providing "partial" support. One interesting thing about this is that taking some strain off the heart might allow the muscle to repair and rebuild its own strength. This process is called reverse remodelling, and is the topic of this research. Our hypothesis is that "partial" support improves patients' symptoms and causes improvement in heart muscle function. We also want to examine the best techniques for assessing this, including new scanning and molecular tests, and study some practical aspects of the pump to do with blood clotting.

Detailed description: The CircuLite Synergy pump is a new minimally-invasive partial support left ventricular assist device (LVAD) that pumps blood from the left atrium to the right subclavian artery. Ex vivo pilot data suggests that the Synergy pump induces structural reverse remodelling, which proposes the Synergy device as a new disease-modifying therapy. We will assess whether the Synergy pump facilitates functional, structural and molecular LV reverse remodelling in vivo; assess how this can be determined and predicted by analysis of circulating micro RNA profiles and specific echocardiographic parameters; and evaluate the haematological abnormalities associated with this new LVAD.

We will address these questions with a prospective, observational study comparing patients implanted with the Synergy device with matched heart failure controls. The two study centres will be Royal Brompton \& Harefield NHS Foundation Trust (Harefield Hospital) and University Hospitals Leuven, Belgium. We will recruit a total of 64 patients. The primary outcome will be change in peak VO2 at 6 months. Secondary outcomes will include functional parameters, profiling of circulating microRNA, multimodal echocardiographic assessment and comprehensive assessment of platelet activation and coagulopathy.

We will quantify the LV reverse remodelling associated with partial support; define new echo and microRNA markers of reverse remodelling for clinical use, with insights into underlying pathophysiology; and describe the haematological profile of these patients to guide future antiplatelet and anticoagulant therapy.

Eligibility criteria: Inclusion Criteria:

* Patients with ischaemic or dilated cardiomyopathy aged 18 to 80 years.
* Symptoms categorised by INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) at level 3-6 despite optimal tolerated medical therapy. Practically this includes patients who are in hospital or managing at home with substantial dependence on hospital care.
* Peak VO2 \<15ml/kg/min with respiratory exchange ratio\>1 on cardiopulmonary exercise testing OR a 6-minute walking distance \<300m OR inability to perform an exercise test due to the severity of heart failure.
* Informed consent obtained prior to entering the study.

Exclusion Criteria:

* Cause of heart failure due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis, or active myocarditis
* Body surface area \<1.2M2 or \>2.3M2, or body mass index \>32 kg/M2.
* Severe chronic obstructive pulmonary disease as evidenced by forced expiratory volume in 1 second \<50% of predicted.
* History of pulmonary hypertension with maintained pulmonary vascular resistance measured \> 4 Wood units or transpulmonary gradient \>14mmHg.
* Pregnancy.
* Evidence of intrinsic hepatic disease defined as liver enzyme levels \> 5 times the upper limit of normal within 4 days before enrolment, severe liver dysfunction, cirrhosis or portal hypertension.
* Occurrence of stroke within 90 days before enrolment.
* Impairment of cognitive function or presence of any form of irreversible dementia.
* Recent history of psychiatric disease (including severe drug or alcohol abuse) that is likely to impair compliance with the study protocol.
* Platelet count \<50 x103mm3 within 24 hours before enrolment.
* Creatinine clearance \< 30ml/min.
* High probability of non-compliance.
* The patient is deemed unsuitable by the clinical team for other reasons.

Primary outcomes:
measure: Change in maximal aerobic exercise capacity (peak VO2)
timeFrame: 6 months
Secondary outcomes:
measure: Change in 6-minute walk distance
timeFrame: 6 months
measure: Change in New York Heart Association (NYHA) functional class
timeFrame: 6 months
measure: Change in B-type natriuretic peptide
timeFrame: 6 months
measure: Change in ventricular dimensions as measured by echocardiography
timeFrame: 6 months
measure: Change in ventricular strain as measured by echocardiography
timeFrame: 6 months
measure: Change in circulating microRNA expression profile
timeFrame: 6 months
measure: Change in ventilatory equivalent for carbon dioxide (VE/VCO2) slope
timeFrame: 6 months
measure: Change in haemodynamic parameters at right heart catheterisation
timeFrame: 6 months
measure: Change in quality of life score
timeFrame: 6 months
measure: Accumulated days of hospital inpatient stay due to cardiovascular reasons
timeFrame: 6 months
measure: Incidence of significant haematological derangements
timeFrame: 6 months
measure: Number of participants suffering adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust
Study officials:
affiliation: Royal Brompton & Harefield NHS Foundation Trust and Imperial College London
name: John R Pepper, FRCS
role: PRINCIPAL_INVESTIGATOR
References: