Lipoprotein Apheresis in Refractory Angina Study

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT01796912
• Collaborator: National Institute for Health Research, United Kingdom (Other)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 33
• Patients Per Site Per Month: 0.6

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Refractory Angina; Raised Lipoprotein(a)>50mg/dL or >500mg/L	Other: Lipoprotein Apheresis; Other: Sham Apheresis	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Clinical Outcomes, Perfusion and Vascular Function in Patients With Refractory Angina and Raised Lipoprotein (a), Treated With Lipoprotein Apheresis
• Actual Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging [3 months]

   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

1. Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging [3 months]

   Changes from baseline to 3 months

2. Change in Endothelial Vascular Function [Within 7 days before and after 3 months of weekly lipoprotein apheresis]

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

3. Change in Seattle Angina Questionnaire Score [3 months]

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

4. Change in SF-36 Quality of Life Score [3 months]

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

5. Change in Exercise Capacity Determined by Six Minute Walk Test [3 months]

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

6. Changes in Markers of Thrombogenesis [3 months]

   Thrombogenesis, Reduce value is better to the patients

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Royal Brompton and Harefield NHS Foundation Trust	London		United Kingdom

Sponsors and Collaborators

• Imperial College London
• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT01796912
• Other Study ID Numbers: 1880
• First Posted: Feb 22, 2013
• Last Update Posted: Nov 12, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: Refractory Angina; Lipoprotein
• Additional relevant MeSH terms: Angina Pectoris

Study Results

Participant Flow

Arm/Group Title	First Lipoprotein Apheresis, Then Sham Apheresis	First Sham Apheresis, Then Lipoprotein Apheresis
Arm/Group Description	Three months of weekly lipoprotein apheresis, 1 month of washout then three month of sham apheresis	Three months of weekly sham apheresis, 1 month of washout then three months of weekly lipoprotein apheresis
Period Title: First Intervention
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participant
Arm/Group Description	Participant were 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 then crossovered to the opposite study arm with the protocol repeated.
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.9 (9.5)
Sex: Female, Male (Count of Participants)
Female	1 5%
Male	19 95%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
United Kingdom	20 100%

Outcome Measures

1. Primary Outcome

Title	Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging
Description	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
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoprotein Apheresis	Sham Apheresis
Arm/Group Description	Three months of weekly lipoprotein apheresis	Three months of weekly sham apheresis
Measure Participants	20	20
Mean (95% Confidence Interval) [ratio]	0.47	-0.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lipoprotein Apheresis, Sham Apheresis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging
Description	Changes from baseline to 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoprotein Apheresis	Sham Apheresis
Arm/Group Description	Lipoprotein Apheresis: Weekly lipoprotein apheresis for 3 months	Sham Apheresis: Weekly sham (placebo) apheresis for 3 months
Measure Participants	20	20
Median (Inter-Quartile Range) [mm3]	-335	127

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lipoprotein Apheresis, Sham Apheresis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoprotein Apheresis	Sham Apheresis
Arm/Group Description	Three months of weekly lipoprotein apheresis	Three months of weekly sham apheresis
Measure Participants	20	20
Mean (95% Confidence Interval) [index]	-0.05	-0.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lipoprotein Apheresis, Sham Apheresis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoprotein Apheresis	Sham Apheresis
Arm/Group Description	Three months of weekly lipoprotein apheresis	Three months of weekly sham apheresis
Measure Participants	20	20
Mean (95% Confidence Interval) [units on a scale]	17.5	-1.75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lipoprotein Apheresis, Sham Apheresis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoprotein Apheresis	Sham Apheresis
Arm/Group Description	Three months of weekly lipoprotein apheresis	Three months of weekly sham apheresis
Measure Participants	20	20
Median (Inter-Quartile Range) [units on a scale]	7.5	-2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lipoprotein Apheresis, Sham Apheresis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoprotein Apheresis	Sham Apheresis
Arm/Group Description	Three months of weekly lipoprotein apheresis	Three months of weekly sham apheresis
Measure Participants	20	20
Median (Inter-Quartile Range) [meter]	70.5	3.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lipoprotein Apheresis, Sham Apheresis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Changes in Markers of Thrombogenesis
Description	Thrombogenesis, Reduce value is better to the patients
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoprotein Apheresis	Sham Apheresis
Arm/Group Description	Three months of weekly lipoprotein apheresis	Three months of weekly sham apheresis
Measure Participants	20	20
Median (Inter-Quartile Range) [seconds]	-355	36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lipoprotein Apheresis, Sham Apheresis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	2 years
Arm/Group Title	Lipoprotein Apheresis		Sham Apheresis
Arm/Group Description	Three months of weekly lipoprotein apheresis		Three months of weekly sham apheresis
All Cause Mortality
	Lipoprotein Apheresis		Sham Apheresis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Lipoprotein Apheresis		Sham Apheresis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Lipoprotein Apheresis		Sham Apheresis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.