Refractory Angina PectorisSCRAPNCT04915157
Efficacy of Spinal Cord Stimulation in Patients With Refractory Angina Pectoris
A study testing Spinal Cord Stimulator in people with Refractory Angina Pectoris and Spinal Cord Stimulation, run by Catharina Ziekenhuis Eindhoven at 1 site in Netherlands.
Trial summary
There are a growing number of patients with refractory angina pectoris (RAP). RAP is defined as a 'chronic condition (> three months) characterized by diffuse coronary artery disease in the presence of proven ischemia, which is not amendable to a combination of medical therapy, angioplasty or coronary bypass surgery'. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Angina Pectoris, Spinal Cord Stimulation
- What is being tested?
- Spinal Cord Stimulator
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteNetherlands
- Study dates
- 21 Dec 2021to Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Refractory Angina Pectoris:
- Stable angina pectoris CCS class III or IV, with a minimum of 5 episodes of angina pectoris over the course of one week, during a minimum period of three months prior to screening
- Coronary angiogram (CAG) performed within the last 12 months showing significant coronary artery disease defined as at least one coronary artery stenosis of >75% or 50 - 75% with proven ischaemia (see below), not suitable for revascularisation. Confirmed by one (or two in case of doubt) interventional cardiologist based on CAG images.
- Optimal anti-anginal medication. Patients should at least use the maximal tolerable dose of a b-blocker, calcium channel blocker and short- and/or long-acting nitrate. If the patient doesn't use one of these groups of medication the reason (side-effects) should be clear.
- Proven ischemia:
- MIBI-SPECT: summed stress score (SSS) of at least 1, in combination with summed difference score (SDS) of at least 1 (1-4 mild ischaemia, > 4 moderate to severe ischaemia).
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- FFR: < 0.80, with no intervention options (determined by interventional cardiologist)
- MRI perfusion: ≥ 1 segment of subendocardial hypoperfusion during stress perfusion, not present at rest and no matching fibrosis (using 16 segment AHA heart model)
- PET: Semi-quantitative measurement: SSS score of at least 1, in combination with SDS score of at least 1 (1-4 mild ischaemia, > 4 moderate to severe ischaemia). Quantitative measurement: reduced myocardial perfusion reserve.
- No revascularisation (PCI and/or CABG) performed between ischaemia testing and study inclusion.
- Age > 18 years
Who cannot join
- Acute coronary syndrome (ACS) during the three month period prior to screening
- Life expectancy less than 12 months
- Inability to perform a 6-minute walking test
- Inability to give informed consent
- No proven ischemia
- Spinal cord disease which could prevent correct positioning of the lead in the epidural space; to be determined by the anaesthesiologist performing the implantation
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- Anticoagulation therapy that cannot be stopped/bridged prior to spinal cord stimulator implantation
- Inadequate paraesthesia coverage, during implantation, of the thoracic region where angina complaints are localized
- Pregnancy
- Mild Cognitive Impairment or dementia
- Concomitant symptomatic valvular heart disease including severe aortic stenosis and/or regurgitation, severe mitral valve stenosis and/or regurgitation or severe tricuspid valve regurgitation.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Catharina Hospital
Eindhoven, North Brabant, 5623EJ
Fabienne E Vervaat, MD, 0031402397000, fabienne.vervaat@catharinaziekenhuis.nl
About this study
Official title: Efficacy of Spinal Cord Stimulation in Patients With Refractory Angina Pectoris; a Randomized Controlled Trial
There are a growing number of patients with refractory angina pectoris (RAP). RAP is defined as a 'chronic condition (> three months) characterized by diffuse coronary artery disease in the presence of proven ischemia, which is not amendable to a combination of medical therapy, angioplasty or coronary bypass surgery'. These patients are severely restricted in performing daily activities due to debilitating angina complaints, leading to a decreased quality of life.
Spinal cord stimulation (SCS) is a last resort treatment option for patients with RAP. SCS is a device with a lead located in the thoracic epidural space and an Implantable Pulse Generator (IPG) in the abdomen or buttock that provides neurostimulation. Four possible mechanisms explaining the beneficial effects of SCS on RAP have been described: reduction of pain perception, decreased sympathetic tone, reduced myocardial oxygen demand, and improved coronary microcirculatory blood flow.
Read more
Research into the effect of SCS on RAP up to date have mainly been observational studies, with only four placebo-controlled randomized controlled trials. All studies confirm that treatment with SCS leads to a reduction in the number of angina pectoris attacks. What is currently not clear, is whether there is a placebo effect as results vary between the studies. One study looked at the effect of SCS in patients with RAP on the reduction of ischemia (using MIBI-SPECT) with no control arm. After 12 months myocardial ischemia was reduced, but not after three months of treatment. Leading to the conclusion that the reduction is myocardial ischemia was not a direct effect of SCS, but rather due to better coronary collateralization.
The 2020 ESC guideline 'chronic coronary syndromes' mentions non-existing to promising levels of evidence with regard to treatment options in patients with RAP and concludes that SCS may be considered (Class IIB; level of evidence B). It concludes that 'larger RCTs are required to define the role of each treatment modality for specific subgroups, to decrease non-responder rates and ascertain benefit beyond potential placebo effects'.
The aim of the current randomized controlled trial (double-blind, cross-over, placebo-controlled, single center) is to determine if high density spinal cord stimulation, a paresthesia free form of stimulation, leads to a significant reduction in myocardial ischemia (using PET with Rubidium-82 as tracer) in patients with refractory angina pectoris.
All patients included in this study will receive an implanted spinal cord stimulator after a positive TENS treadmill outcome and proven ischemia using the imaging modality PET with Rubidium-82 as tracer. Using a cross-over design all patients will have a 6 month period with high density stimulation and 6 month period of no stimulation. Randomization will determine in which order the patient receives these treatments. Both the patient and the treating physicians are blinded for this randomization process. At baseline a 6-minute walking test, the Seattle Angina Questionnaire, the RAND-36 questionnaire, the NRS scale and the CCS class will be performed/filled out.
Cross-over takes place at 6 months (switch from high density stimulation to no stimulation or vice versa) prior to which the PET scan is repeated, as well as the 6-minute walking test, the Seattle Angina Questionnaire, the RAND-36 questionnaire, the NRS-scale and the CCS-class.
At the end of the study period (12 months) the PET scan is repeated, as well as the 6-minute walking test, the Seattle Angina Questionnaire, the RAND-36 questionnaire, the NRS-scale and the CCS-class.
- Being tested
- Spinal Cord Stimulator
- Medical subject headings
- Angina Pectoris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Spinal Cord StimulatorDevice
Also called Medtronic PrimeADVANCED™ SureScan® myStim & Vectris Compact™ SureScan MRI electrode
All patients will receive an implanted spinal cord stimulator.
| Study group | Role | What they receive |
|---|---|---|
| Group A: High Density stimulation - No Stimulation | Other | Patients in this group will receive high density stimulation (parasthesia free form of stimulation) during the first 6 months of the study period. After 6 months cross-over will take place and patients will receive no stimulation during the final 6 months of the study period. Receives: Device: Spinal Cord Stimulator |
| Group B: No Stimulation - High Density Stimulation | Other | Patients in this group will receive no stimulation during the first 6 months of the study period. After 6 months cross-over will take place and patients will receive high density stimulation (parasthesia free form of stimulation) during the final 6 months of the study period. Receives: Device: Spinal Cord Stimulator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial ischaemia
The primary endpoint is the change in the percentage of myocardial ischaemia (% of left ventricular myocardium) measured using PET perfusion scan at the end of the six month period of HD stimulation compared to baseline.
Measured: 6 months
Secondary outcomes (11)
Patient condition
Patient condition measured using the 6-minute walking test
Measured: From date of randomization until six and twelve months later
Frequency of angina pectoris attacks
Frequency of angina pectoris attacks measured using the Seattle Angina Questionnaire; scale 0 - 100 with higher scores representing a better outcome.
Measured: From date of randomization until six and twelve months later
Severity of angina pectoris attacks
Severity of angina pectoris attacks using the Numeric Rating Scale (NRS-scale); scale 0 - 10 with higher scores representing a worse outcome.
Measured: From date of randomization until six and twelve months later
Grading of angina pectoris
Grading of angina pectoris using the Canadian Cardiovascular Society (CCS) class; grading scale of I - IV with higher scores representing worse outcome.
Measured: From date of randomization until six and twelve months later
Frequency of short-acting nitroglycerin use
Frequency of short-acting nitroglycerin use measured using the Seattle Angina Questionnaire; scale 0 - 100 with higher scores representing a better outcome.
Measured: From date of randomization until six and twelve months later
Quality of life outcome
Quality of life outcome measured using the RAND 36-Item Health Survery (RAND-36 questionnaire); scale 0 - 100 with higher scores representing a better outcome.
Measured: From date of randomization until six and twelve months later
Hospital admissions due to acute coronary syndrome
Number of hospital admissions due to acute coronary syndrome (ACS)
Measured: From date of randomization until six and twelve months later
Revascularization
Occurence of revascularization (CABG and/or PCI)
Measured: From date of randomization until six and twelve months later
Emergency room visits due to angina pectoris
Number of presentations at the emergency room due to angina pectoris
Measured: From date of randomization until six and twelve months later
Cardiovascular mortality
Occurence of cardiovascular mortality
Measured: From date of randomization until six and twelve months later
Changes in regional and global myocardial blood flow and myocardial flow reserve
Changes in the regional and global myocardial blood flow and myocardial flow reserve measured using PET perfusion scan
Measured: From date of randomization until six and twelve months later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2021
- Study start21 Dec 2021
- Primary completionJun 2024 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Refractory Angina PectorisStudies of the same condition, open and under way.
- 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
- Parallel groups
- Model description
- Patients will be randomized in a 1:1 fashion to either Group A (High Density stimulation - No stimulation) or Group B (No stimulation - High Density stimulation). All patients will receive an implanted spinal cord stimulator.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Catharina Ziekenhuis Eindhoven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Inge Wijnbergen, Catharina Ziekenhuis Eindhoven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04915157
- Sponsor's protocol ID
- SCRAP
- Acronym
- SCRAP
- Status last verified
- Aug 2023
- First submitted
- 11 May 2021
- Last updated
- 1 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Vervaat FE, van der Gaag A, Smetsers C, Barneveld PC, Van't Veer M, Teeuwen K, van Suijlekom H, Dekker L, Wijnbergen IF. Design and rationale of the efficacy of spinal cord stimulation in patients with refractory angina pectoris (SCRAP) trial. Clin Cardiol. 2023 Jun;46(6):689-697. doi: 10.1002/clc.24016. Epub 2023 Apr 4.
PubMed 37013654
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Spinal Cord Stimulation in Patients With Refractory Angina Pectoris; a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04915157
- Acronym / sponsor ID
- SCRAP / SCRAP
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Catharina Ziekenhuis EindhovenUniversity, hospital or other
- Study start
- 21 Dec 2021 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 7 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There are a growing number of patients with refractory angina pectoris (RAP). RAP is defined as a 'chronic condition (> three months) characterized by diffuse coronary artery disease in the presence of proven ischemia, which is not amendable to a combination of medical therapy, angioplasty or coronary bypass surgery'. These patients are severely restricted in performing daily activities due to debilitating angina complaints, leading to a decreased quality of life.
Spinal cord stimulation (SCS) is a last resort treatment option for patients with RAP. SCS is a device with a lead located in the thoracic epidural space and an Implantable Pulse Generator (IPG) in the abdomen or buttock that provides neurostimulation. Four possible mechanisms explaining the beneficial effects of SCS on RAP have been described: reduction of pain perception, decreased sympathetic tone, reduced myocardial oxygen demand, and improved coronary microcirculatory blood flow.
Research into the effect of SCS on RAP up to date have mainly been observational studies, with only four placebo-controlled randomized controlled trials. All studies confirm that treatment with SCS leads to a reduction in the number of angina pectoris attacks. What is currently not clear, is whether there is a placebo effect as results vary between the studies. One study looked at the effect of SCS in patients with RAP on the reduction of ischemia (using MIBI-SPECT) with no control arm. After 12 months myocardial ischemia was reduced, but not after three months of treatment. Leading to the conclusion that the reduction is myocardial ischemia was not a direct effect of SCS, but rather due to better coronary collateralization.
The 2020 ESC guideline 'chronic coronary syndromes' mentions non-existing to promising levels of evidence with regard to treatment options in patients with RAP and concludes that SCS may be considered (Class IIB; level of evidence B). It concludes that 'larger RCTs are required to define the role of each treatment modality for specific subgroups, to decrease non-responder rates and ascertain benefit beyond potential placebo effects'.
The aim of the current randomized controlled trial (double-blind, cross-over, placebo-controlled, single center) is to determine if high density spinal cord stimulation, a paresthesia free form of stimulation, leads to a significant reduction in myocardial ischemia (using PET with Rubidium-82 as tracer) in patients with refractory angina pectoris.
All patients included in this study will receive an implanted spinal cord stimulator after a positive TENS treadmill outcome and proven ischemia using the imaging modality PET with Rubidium-82 as tracer. Using a cross-over design all patients will have a 6 month period with high density stimulation and 6 month period of no stimulation. Randomization will determine in which order the patient receives these treatments. Both the patient and the treating physicians are blinded for this randomization process. At baseline a 6-minute walking test, the Seattle Angina Questionnaire, the RAND-36 questionnaire, the NRS scale and the CCS class will be performed/filled out.
Cross-over takes place at 6 months (switch from high density stimulation to no stimulation or vice versa) prior to which the PET scan is repeated, as well as the 6-minute walking test, the Seattle Angina Questionnaire, the RAND-36 questionnaire, the NRS-scale and the CCS-class.
At the end of the study period (12 months) the PET scan is repeated, as well as the 6-minute walking test, the Seattle Angina Questionnaire, the RAND-36 questionnaire, the NRS-scale and the CCS-class.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomized in a 1:1 fashion to either Group A (High Density stimulation - No stimulation) or Group B (No stimulation - High Density stimulation). All patients will receive an implanted spinal cord stimulator.
| Arm | Type | Receives |
|---|---|---|
| Group A: High Density stimulation - No Stimulation | Other | Device: Spinal Cord StimulatorPatients in this group will receive high density stimulation (parasthesia free form of stimulation) during the first 6 months of the study period. After 6 months cross-over will take place and patients will receive no stimulation during the final 6 months of the study period. |
| Group B: No Stimulation - High Density Stimulation | Other | Device: Spinal Cord StimulatorPatients in this group will receive no stimulation during the first 6 months of the study period. After 6 months cross-over will take place and patients will receive high density stimulation (parasthesia free form of stimulation) during the final 6 months of the study period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Refractory Angina Pectoris:
- Proven ischemia:
- No revascularisation (PCI and/or CABG) performed between ischaemia testing and study inclusion.
- Age > 18 years
Key exclusion criteria (11 listed)
- Acute coronary syndrome (ACS) during the three month period prior to screening
- Life expectancy less than 12 months
- Inability to perform a 6-minute walking test
- Inability to give informed consent
- No proven ischemia
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 |
|---|---|---|
| Spinal Cord StimulatorAlso: Medtronic PrimeADVANCED™ SureScan® myStim & Vectris Compact™ SureScan MRI electrodeAll patients will receive an implanted spinal cord stimulator. | Device | Group A: High Density stimulation - No Stimulation, Group B: No Stimulation - High Density Stimulation |
Primary outcome
Myocardial ischaemia
Time frame: 6 months
The primary endpoint is the change in the percentage of myocardial ischaemia (% of left ventricular myocardium) measured using PET perfusion scan at the end of the six month period of HD stimulation compared to baseline.
11 secondary outcomes
Patient condition
Time frame: From date of randomization until six and twelve months later
Frequency of angina pectoris attacks
Time frame: From date of randomization until six and twelve months later
Severity of angina pectoris attacks
Time frame: From date of randomization until six and twelve months later
Grading of angina pectoris
Time frame: From date of randomization until six and twelve months later
Frequency of short-acting nitroglycerin use
Time frame: From date of randomization until six and twelve months later
Quality of life outcome
Time frame: From date of randomization until six and twelve months later
Hospital admissions due to acute coronary syndrome
Time frame: From date of randomization until six and twelve months later
Revascularization
Time frame: From date of randomization until six and twelve months later
Emergency room visits due to angina pectoris
Time frame: From date of randomization until six and twelve months later
Cardiovascular mortality
Time frame: From date of randomization until six and twelve months later
Changes in regional and global myocardial blood flow and myocardial flow reserve
Time frame: From date of randomization until six and twelve months later
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
- Derived from this study: PubMed 37013654Vervaat FE, van der Gaag A, Smetsers C, Barneveld PC, Van't Veer M, Teeuwen K, van Suijlekom H, Dekker L, Wijnbergen IF. Design and rationale of the efficacy of spinal cord stimulation in patients with refractory angina pectoris (SCRAP) trial. Clin Cardiol. 2023 Jun;46(6):689-697. doi: 10.1002/clc.24016. Epub 2023 Apr 4.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Spinal Cord Stimulator in people with Refractory Angina Pectoris and Spinal Cord Stimulation, run by Catharina Ziekenhuis Eindhoven at 1 site in Netherlands.
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 11 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 1 Sep 2023. 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 Netherlands. 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Inge Wijnbergen, MD, PhD (0031402397000, inge.wijnbergen@catharinaziekenhuis.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Myocardial ischaemia (time frame: 6 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 NCT04915157, 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 1 Sep 2023.