Refractory AnginaNCT01796912
Lipoprotein Apheresis in Refractory Angina Study
A study testing Lipoprotein Apheresis in people with Refractory Angina and Raised Lipoprotein(a)>50mg/dL or >500mg/L, run by Imperial College London at 1 site in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Refractory Angina, Raised Lipoprotein(a)>50mg/dL or >500mg/L
- What is being tested?
- Lipoprotein Apheresis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2013to Nov 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Brompton and Harefield NHS Foundation Trust
London
About this study
Official title: 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.
Read the 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.
- Being tested
- Lipoprotein Apheresis, Sham Apheresis
- Keywords
- Refractory Angina, Lipoprotein
- Medical subject headings
- Angina Pectoris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lipoprotein ApheresisOther
Weekly lipoprotein apheresis for 3 months
Sham ApheresisOther
Weekly sham (placebo) apheresis for 3 months
| Study group | Role | What they receive |
|---|---|---|
| First Lipoprotein Apheresis, then sham apheresis | Active comparator | Three months of weekly lipoprotein apheresis, 1 month washout, then three month sham apheresis Receives: Other: Lipoprotein Apheresis |
| First Sham Apheresis, then Lipoprotein Apheresis | Sham comparator | Three months of weekly sham apheresis, 1 month washout, then three month lipoprotein Apheresis Receives: Other: Sham Apheresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 months
Secondary outcomes (6)
Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging
Changes from baseline to 3 months
Measured: 3 months
Change in Endothelial Vascular Function
EndoPat LnRHI - natural logarithm of reactive hyperaemia index. Increase - better outcome
Measured: 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
Measured: 3 months
Change in SF-36 Quality of Life Score
Quality of Life score following, 0-100 score, high score improve quality of life
Measured: 3 months
Change in Exercise Capacity Determined by Six Minute Walk Test
Six minute walk test, patient can walk longer distance means improvements
Measured: 3 months
Changes in Markers of Thrombogenesis
Thrombogenesis, Reduce value is better to the patients
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Refractory AnginaStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Dudley Pennell, MB BChir MA MD FRCP, Principal investigator, Imperial College LondonMahmoud Barbir, MB BCh, FRCP, Study director, Royal Brompton and Harfield Hospital, Imperial College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01796912
- Sponsor's protocol ID
- 1880
- Status last verified
- Oct 2019
- First submitted
- 15 Feb 2013
- Last updated
- 12 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 28453721
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Outcomes, Perfusion and Vascular Function in Patients With Refractory Angina and Raised Lipoprotein (a), Treated With Lipoprotein Apheresis
- ClinicalTrials.gov ID
- NCT01796912
- Acronym / sponsor ID
- 1880
- Keywords
- Refractory Angina, Lipoprotein
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Study start
- Feb 2013 (actual)
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 22 Feb 2013 (estimated)
- Results
- Posted 12 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| First Lipoprotein Apheresis, then sham apheresis | Active comparator | Other: Lipoprotein ApheresisThree months of weekly lipoprotein apheresis, 1 month washout, then three month sham apheresis |
| First Sham Apheresis, then Lipoprotein Apheresis | Sham comparator | Other: Sham ApheresisThree months of weekly sham apheresis, 1 month washout, then three month lipoprotein Apheresis |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lipoprotein ApheresisWeekly lipoprotein apheresis for 3 months | Other | First Lipoprotein Apheresis, then sham apheresis |
| Sham ApheresisWeekly sham (placebo) apheresis for 3 months | Other | First Sham Apheresis, then Lipoprotein Apheresis |
Primary outcome
Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging
Time frame: 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
6 secondary outcomes
Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging
Time frame: 3 months
Change in Endothelial Vascular Function
Time frame: Within 7 days before and after 3 months of weekly lipoprotein apheresis
Change in Seattle Angina Questionnaire Score
Time frame: 3 months
Change in SF-36 Quality of Life Score
Time frame: 3 months
Change in Exercise Capacity Determined by Six Minute Walk Test
Time frame: 3 months
Changes in Markers of Thrombogenesis
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28453721Khan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dudley Pennell, MB BChir MA MD FRCP principal investigator
Imperial College London
Mahmoud Barbir, MB BCh, FRCP study director
Royal Brompton and Harfield Hospital, Imperial College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lipoprotein Apheresis in people with Refractory Angina and Raised Lipoprotein(a)>50mg/dL or >500mg/L, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01796912, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2019; AzTrials last refreshed its copy on 30 Oct 2026.