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Lipoprotein Apheresis in Refractory Angina Study

Primary Purpose

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

Status

Completed

Phase

Not Applicable

Locations

United Kingdom

Study Type

Interventional

Intervention

Lipoprotein Apheresis

Sham Apheresis

About this trial

This is an interventional treatment trial for Refractory Angina focused on measuring Refractory Angina, Lipoprotein

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Royal Brompton and Harefield NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

First Lipoprotein Apheresis, then sham apheresis

First Sham Apheresis, then Lipoprotein Apheresis

Arm Description

Three months of weekly lipoprotein apheresis, 1 month washout, then three month sham apheresis

Three months of weekly sham apheresis, 1 month washout, then three month lipoprotein Apheresis

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging

Changes from baseline to 3 months

Change in Endothelial Vascular Function

EndoPat LnRHI - natural logarithm of reactive hyperaemia index. Increase - better outcome

Change in Seattle Angina Questionnaire Score

SAQ-Angina stability, increase means improvement. 0-100 scale, Higher score means improvements

Change in SF-36 Quality of Life Score

Quality of Life score following, 0-100 score, high score improve quality of life

Change in Exercise Capacity Determined by Six Minute Walk Test

Six minute walk test, patient can walk longer distance means improvements

Changes in Markers of Thrombogenesis

Thrombogenesis, Reduce value is better to the patients

Full Information

NCT ID

NCT01796912

First Posted

February 15, 2013

Last Updated

October 21, 2019

Sponsor

Imperial College London

Collaborators

National Institute for Health Research, United Kingdom

1. Study Identification

Unique Protocol Identification Number

NCT01796912

Brief Title

Lipoprotein Apheresis in Refractory Angina Study

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

February 2013 (Actual)

Primary Completion Date

November 2015 (Actual)

Study Completion Date

November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Imperial College London

Collaborators

National Institute for Health Research, United Kingdom

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Refractory Angina, Lipoprotein

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

Participant

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

First Lipoprotein Apheresis, then sham apheresis

Arm Type

Active Comparator

Arm Description

Three months of weekly lipoprotein apheresis, 1 month washout, then three month sham apheresis

Arm Title

First Sham Apheresis, then Lipoprotein Apheresis

Arm Type

Sham Comparator

Arm Description

Three months of weekly sham apheresis, 1 month washout, then three month lipoprotein Apheresis

Intervention Type

Other

Intervention Name(s)

Lipoprotein Apheresis

Intervention Description

Weekly lipoprotein apheresis for 3 months

Intervention Type

Other

Intervention Name(s)

Sham Apheresis

Intervention Description

Weekly sham (placebo) apheresis for 3 months

Primary Outcome Measure Information:

Title

Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging

Description

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging

Description

Changes from baseline to 3 months

Time Frame

3 months

Title

Change in Endothelial Vascular Function

Description

EndoPat LnRHI - natural logarithm of reactive hyperaemia index. Increase - better outcome

Time Frame

Within 7 days before and after 3 months of weekly lipoprotein apheresis

Title

Change in Seattle Angina Questionnaire Score

Description

SAQ-Angina stability, increase means improvement. 0-100 scale, Higher score means improvements

Time Frame

3 months

Title

Change in SF-36 Quality of Life Score

Description

Quality of Life score following, 0-100 score, high score improve quality of life

Time Frame

3 months

Title

Change in Exercise Capacity Determined by Six Minute Walk Test

Description

Six minute walk test, patient can walk longer distance means improvements

Time Frame

3 months

Title

Changes in Markers of Thrombogenesis

Description

Thrombogenesis, Reduce value is better to the patients

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dudley Pennell, MB BChir MA MD FRCP

Organizational Affiliation

Imperial College London

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Mahmoud Barbir, MB BCh, FRCP

Organizational Affiliation

Royal Brompton and Harfield Hospital, Imperial College

Official's Role

Study Director

Facility Information:

Facility Name

Royal Brompton and Harefield NHS Foundation Trust

City

London

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

28453721

Citation

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.

Results Reference

result

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Lipoprotein Apheresis in Refractory Angina Study

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