Lipoprotein Apheresis in Refractory Angina Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Imperial College London
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01796912
First received: February 15, 2013
Last updated: February 20, 2013
Last verified: February 2013
  Purpose

Angina which is refractory to conventional medical therapy and revascularisation is challenging to manage. Lipoprotein(a) or Lp(a) is a genetically determined form of LDL-cholesterol, elevation of which is an independent risk factor and predictor of adverse cardiovascular events. Lp(a) is felt to increase cardiovascular risk via its prothrombotic effect and by enhancing intimal lipoprotein deposition. Lipoprotein apheresis is the most effective treatment for raised Lp(a). Lipid lowering agents such as statins have little to no effect on Lp(a) levels.

The goal of this study is to determine the impact of apheresis on clinical parameters and symptoms of patients with refractory angina and raised Lp(a). The investigators will conduct a prospective, randomised controlled crossover study of 20 patients with refractory angina and raised Lp(a), randomised to undergoing lipoprotein apheresis weekly for three months or sham apheresis weekly for three months with assessment of myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, exercise capacity, angina symptoms and quality of life at the beginning and end of treatment. Patients will then crossover to the opposite study arm with the protocol repeated. The hypothesis is that the above parameters will be improved by lipoprotein apheresis in patients with raised Lp(a) and Refractory Angina. Investigators will also test for the genotypic presence of LPA locus variants (rs10455872 and rs3798220) which are thought to be associated with an increased level of Lp(a) and an increased risk of coronary disease.


Condition Intervention
Refractory Angina
Raised Lipoprotein(a)>50mg/dL or >500mg/L
Other: Lipoprotein Apheresis
Other: Sham Apheresis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Clinical Outcomes, Perfusion and Vascular Function in Patients With Refractory Angina and Raised Lipoprotein (a), Treated With Lipoprotein Apheresis

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Change in Quantitative myocardial perfusion measured by stress/rest cardiovascular magnetic resonance imaging following 3 months weekly apheresis compared to baseline. [ Time Frame: Within 7 days before and after three months of weekly apheresis ] [ Designated as safety issue: No ]
    Investigators will determine the impact of lipoprotein apheresis on quantitative myocardial perfusion measured by stress/rest cardiovascular magnetic resonance imaging at baseline and after 3 months of weekly lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a). This will be compared to quantitative perfusion before and after 3 months of sham apheresis.


Secondary Outcome Measures:
  • Change in Carotid Atherosclerosis/plaque burden determined by Cardiovascular Magnetic Resonance Imaging following 3 months weekly apheresis compared to baseline. [ Time Frame: Within 7 days before and after 3 months of weekly lipoprotein apheresis ] [ Designated as safety issue: No ]
  • Change in Endothelial vascular function following 3 months weekly apheresis compared to baseline. [ Time Frame: Within 7 days before and after 3 months of weekly lipoprotein apheresis ] [ Designated as safety issue: No ]
  • Change in Seattle Angina Questionnaire Score following 3 months weekly apheresis compared to baseline. [ Time Frame: Within 7 days before and after 3 months of weekly lipoprotein apheresis ] [ Designated as safety issue: No ]
  • Change in SF-36 Quality of Life score following 3 months weekly apheresis compared to baseline. [ Time Frame: Within 7 days before and after 3 months of weekly lipoprotein apheresis ] [ Designated as safety issue: No ]
  • Change in Exercise capacity determined by six minute walk test following 3 months weekly apheresis compared to baseline. [ Time Frame: Within 7 days before and after 3 months of weekly lipoprotein apheresis ] [ Designated as safety issue: No ]
  • Changes in Markers of Thrombogenesis following 3 months weekly apheresis compared to baseline. [ Time Frame: Within 24 hours before and after 3 months of weekly lipoprotein apheresis ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: February 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lipoprotein Apheresis
Three months of weekly lipoprotein apheresis
Other: Lipoprotein Apheresis
Sham Comparator: Sham Apheresis
Three months of weekly sham apheresis
Other: Sham Apheresis

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients diagnosed with refractory angina for more than three months.
  • Two or more episodes of angina per week.
  • Previous history of myocardial infarction, coronary artery bypass graft (CABG) surgery,percutaneous coronary intervention (PCI) or any combination of the above.
  • Prescribed optimal medical therapy.
  • Hypercholesterolaemia with an elevated Lp(a) > 50mg/dL and an LDL-cholesterol less than 4.0mmol/L despite optimal lipid lowering drug therapy.

Exclusion Criteria:

  • Patients with poor calibre veins for cannulation.
  • Patients with any other chronic systemic illness such as liver or renal failure, neoplastic disease, overt cardiac failure, unstable coronary artery disease, coronary revascularisation or a myocardial infarction within the previous eight weeks.
  • Pregnancy, untreated diabetes mellitus, untreated arterial hypertension, and those with general contraindications to undergoing Cardiovascular magnetic resonance imaging or contraindications to adenosine.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01796912

Contacts
Contact: Mahmoud Barbir, MB BCh BAO LRCP&SI FRCP 07767823790 M.Barbir@rbht.nhs.uk

Locations
United Kingdom
Royal Brompton and Harefield NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Tina Khan, MRCP MBChB BHB       T.Khan@rbht.nhs.uk   
Principal Investigator: Dudley Pennell, MB BChir MA MD FRCP FACC FESC         
Sub-Investigator: Mahmoud Barbir, MB BCh BAO LRCP&SI FRCP         
Sub-Investigator: Tina Khan, MRCP MBChB BHB         
Sponsors and Collaborators
Imperial College London
National Institute for Health Research, United Kingdom
Investigators
Principal Investigator: Dudley Pennell, MB BChir MA MD FRCP FACC FESC Imperial College London
Study Director: Mahmoud Barbir, MB BCh BAO LRCP&SI FRCP Royal Brompton and Harfield Hospital, Imperial College
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01796912     History of Changes
Other Study ID Numbers: 1880
Study First Received: February 15, 2013
Last Updated: February 20, 2013
Health Authority: United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Angina Pectoris
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on July 26, 2014