Lipoprotein Apheresis in Refractory Angina Study

Clinical Outcomes, Perfusion and Vascular Function in Patients With Refractory Angina and Raised Lipoprotein (a), Treated With Lipoprotein Apheresis

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 apolipoprotein(a) gene (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.

Study Overview

• Status: Completed
• Conditions: Refractory Angina; Raised Lipoprotein(a)>50mg/dL or >500mg/L
• Intervention / Treatment: Other: Lipoprotein Apheresis; Other: Sham Apheresis

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Royal Brompton and Harefield NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: First Lipoprotein Apheresis, then sham apheresis; Three months of weekly lipoprotein apheresis, 1 month washout, then three month sham apheresis	Other: Lipoprotein Apheresis; Weekly lipoprotein apheresis for 3 months
Sham Comparator: First Sham Apheresis, then Lipoprotein Apheresis; Three months of weekly sham apheresis, 1 month washout, then three month lipoprotein Apheresis	Other: Sham Apheresis; Weekly sham (placebo) apheresis for 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging	Baseline compare to 3 month, changes presented Determine the impact of lipoprotein apheresis on quantitative myocardial perfusion measured by stress/rest cardiovascular magnetic resonance imaging. Increase means better outcome	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging	Changes from baseline to 3 months	3 months
Change in Endothelial Vascular Function	EndoPat LnRHI - natural logarithm of reactive hyperaemia index. Increase - better outcome	Within 7 days before and after 3 months of weekly lipoprotein apheresis
Change in Seattle Angina Questionnaire Score	SAQ-Angina stability, increase means improvement. 0-100 scale, Higher score means improvements	3 months
Change in SF-36 Quality of Life Score	Quality of Life score following, 0-100 score, high score improve quality of life	3 months
Change in Exercise Capacity Determined by Six Minute Walk Test	Six minute walk test, patient can walk longer distance means improvements	3 months
Changes in Markers of Thrombogenesis	Thrombogenesis, Reduce value is better to the patients	3 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Dudley Pennell, MB BChir MA MD FRCP, Imperial College London; Study Director: Mahmoud Barbir, MB BCh, FRCP, Royal Brompton and Harfield Hospital, Imperial College

Publications and helpful links

General Publications

• Khan TZ, Hsu LY, Arai AE, Rhodes S, Pottle A, Wage R, Banya W, Gatehouse PD, Giri S, Collins P, Pennell DJ, Barbir M. Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a randomized controlled cross-over trial. Eur Heart J. 2017 May 21;38(20):1561-1569. doi: 10.1093/eurheartj/ehx178.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2013
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: February 15, 2013
• First Submitted That Met QC Criteria: February 20, 2013
• First Posted (Estimate): February 22, 2013

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: October 21, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Refractory Angina; Lipoprotein
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris
• Other Study ID Numbers: 1880

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No