Lipoprotein Apheresis in Refractory Angina Study

Refractory Angina Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01796912
• Other study ID #: 1880
• Status: Completed
• Phase: N/A
• Start date: February 2013
• Est. completion date: November 2015

Study information

• Verified date: October 2019
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Angina Pectoris
• Raised Lipoprotein(a)>50mg/dL or >500mg/L
• Refractory Angina

Intervention

Other:
• Lipoprotein Apheresis
Weekly lipoprotein apheresis for 3 months
• Sham Apheresis
Weekly sham (placebo) apheresis for 3 months

Locations

Country	Name	City	State
United Kingdom	Royal Brompton and Harefield NHS Foundation Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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. 201 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging	Changes from baseline to 3 months	3 months
Secondary	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
Secondary	Change in Seattle Angina Questionnaire Score	SAQ—Angina stability, increase means improvement. 0-100 scale, Higher score means improvements	3 months
Secondary	Change in SF-36 Quality of Life Score	Quality of Life score following, 0-100 score, high score improve quality of life	3 months
Secondary	Change in Exercise Capacity Determined by Six Minute Walk Test	Six minute walk test, patient can walk longer distance means improvements	3 months
Secondary	Changes in Markers of Thrombogenesis	Thrombogenesis, Reduce value is better to the patients	3 months