Efficacy of Spinal Cord Stimulation in Patients With Refractory Angina Pectoris (SCRAP)

August 31, 2023 updated by: Inge Wijnbergen, Catharina Ziekenhuis Eindhoven

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.

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

72

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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).
    • 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

Exclusion Criteria:

  • 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
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Group A: High Density stimulation - No Stimulation
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.
Device: Spinal Cord Stimulator
All patients will receive an implanted spinal cord stimulator.
Other Names:
  • Medtronic PrimeADVANCED™ SureScan® myStim & Vectris Compact™ SureScan MRI electrode
Other: Group B: No Stimulation - High Density Stimulation
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.
Device: Spinal Cord Stimulator
All patients will receive an implanted spinal cord stimulator.
Other Names:
  • Medtronic PrimeADVANCED™ SureScan® myStim & Vectris Compact™ SureScan MRI electrode

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient condition
Time Frame: From date of randomization until six and twelve months later
Patient condition measured using the 6-minute walking test
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
Frequency of angina pectoris attacks measured using the Seattle Angina Questionnaire; scale 0 - 100 with higher scores representing a better outcome.
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
Severity of angina pectoris attacks using the Numeric Rating Scale (NRS-scale); scale 0 - 10 with higher scores representing a worse outcome.
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
Grading of angina pectoris using the Canadian Cardiovascular Society (CCS) class; grading scale of I - IV with higher scores representing worse outcome.
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
Frequency of short-acting nitroglycerin use measured using the Seattle Angina Questionnaire; scale 0 - 100 with higher scores representing a better outcome.
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
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.
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
Number of hospital admissions due to acute coronary syndrome (ACS)
From date of randomization until six and twelve months later
Revascularization
Time Frame: From date of randomization until six and twelve months later
Occurence of revascularization (CABG and/or PCI)
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
Number of presentations at the emergency room due to angina pectoris
From date of randomization until six and twelve months later
Cardiovascular mortality
Time Frame: From date of randomization until six and twelve months later
Occurence of cardiovascular mortality
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
Changes in the regional and global myocardial blood flow and myocardial flow reserve measured using PET perfusion scan
From date of randomization until six and twelve months later

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Device infection
Time Frame: From date of randomization until six and twelve months later
Number of device infections (lead and/or battery)
From date of randomization until six and twelve months later
Device dislocation
Time Frame: From date of randomization until six and twelve months later
Number of device dislocations (lead and/or battery)
From date of randomization until six and twelve months later
Lead fractures
Time Frame: From date of randomization until six and twelve months later
Number of lead fractures/breakages
From date of randomization until six and twelve months later
Lead failure
Time Frame: From date of randomization until six and twelve months later
Number of lead failures
From date of randomization until six and twelve months later
Battery End of Life (EOL)
Time Frame: From date of randomization until six and twelve months later
Number of battery End of Life (EOL)
From date of randomization until six and twelve months later

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Catharina Ziekenhuis Eindhoven

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2021

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

May 11, 2021

First Submitted That Met QC Criteria

May 31, 2021

First Posted (Actual)

June 7, 2021

Study Record Updates

Last Update Posted (Actual)

September 1, 2023

Last Update Submitted That Met QC Criteria

August 31, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCRAP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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