search
Back to results

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

Primary Purpose

Refractory Angina Pectoris, Spinal Cord Stimulation

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Spinal Cord Stimulator
Sponsored by
Catharina Ziekenhuis Eindhoven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Angina Pectoris

Eligibility Criteria

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

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.

Sites / Locations

  • Catharina HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Group A: High Density stimulation - No Stimulation

Group B: No Stimulation - High Density Stimulation

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Patient condition
Patient condition measured using the 6-minute walking test
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.
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.
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.
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.
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.
Hospital admissions due to acute coronary syndrome
Number of hospital admissions due to acute coronary syndrome (ACS)
Revascularization
Occurence of revascularization (CABG and/or PCI)
Emergency room visits due to angina pectoris
Number of presentations at the emergency room due to angina pectoris
Cardiovascular mortality
Occurence of cardiovascular mortality
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

Full Information

First Posted
May 11, 2021
Last Updated
August 31, 2023
Sponsor
Catharina Ziekenhuis Eindhoven
search

1. Study Identification

Unique Protocol Identification Number
NCT04915157
Brief Title
Efficacy of Spinal Cord Stimulation in Patients With Refractory Angina Pectoris
Acronym
SCRAP
Official Title
Efficacy of Spinal Cord Stimulation in Patients With Refractory Angina Pectoris; a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 21, 2021 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Catharina Ziekenhuis Eindhoven

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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'. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Angina Pectoris, Spinal Cord Stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
One nurse will perform the randomization and know to which group the patient was randomized. The same nurse will input the correct settings into the spinal cord stimulator. The other investigators, the participant, care provider and outcomes assessor will remain masked during the study period.
Allocation
Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A: High Density stimulation - No Stimulation
Arm Type
Other
Arm Description
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.
Arm Title
Group B: No Stimulation - High Density Stimulation
Arm Type
Other
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Spinal Cord Stimulator
Other Intervention Name(s)
Medtronic PrimeADVANCED™ SureScan® myStim & Vectris Compact™ SureScan MRI electrode
Intervention Description
All patients will receive an implanted spinal cord stimulator.
Primary Outcome Measure Information:
Title
Myocardial ischaemia
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Patient condition
Description
Patient condition measured using the 6-minute walking test
Time Frame
From date of randomization until six and twelve months later
Title
Frequency of angina pectoris attacks
Description
Frequency of angina pectoris attacks measured using the Seattle Angina Questionnaire; scale 0 - 100 with higher scores representing a better outcome.
Time Frame
From date of randomization until six and twelve months later
Title
Severity of angina pectoris attacks
Description
Severity of angina pectoris attacks using the Numeric Rating Scale (NRS-scale); scale 0 - 10 with higher scores representing a worse outcome.
Time Frame
From date of randomization until six and twelve months later
Title
Grading of angina pectoris
Description
Grading of angina pectoris using the Canadian Cardiovascular Society (CCS) class; grading scale of I - IV with higher scores representing worse outcome.
Time Frame
From date of randomization until six and twelve months later
Title
Frequency of short-acting nitroglycerin use
Description
Frequency of short-acting nitroglycerin use measured using the Seattle Angina Questionnaire; scale 0 - 100 with higher scores representing a better outcome.
Time Frame
From date of randomization until six and twelve months later
Title
Quality of life outcome
Description
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.
Time Frame
From date of randomization until six and twelve months later
Title
Hospital admissions due to acute coronary syndrome
Description
Number of hospital admissions due to acute coronary syndrome (ACS)
Time Frame
From date of randomization until six and twelve months later
Title
Revascularization
Description
Occurence of revascularization (CABG and/or PCI)
Time Frame
From date of randomization until six and twelve months later
Title
Emergency room visits due to angina pectoris
Description
Number of presentations at the emergency room due to angina pectoris
Time Frame
From date of randomization until six and twelve months later
Title
Cardiovascular mortality
Description
Occurence of cardiovascular mortality
Time Frame
From date of randomization until six and twelve months later
Title
Changes in regional and global myocardial blood flow and myocardial flow reserve
Description
Changes in the regional and global myocardial blood flow and myocardial flow reserve measured using PET perfusion scan
Time Frame
From date of randomization until six and twelve months later
Other Pre-specified Outcome Measures:
Title
Device infection
Description
Number of device infections (lead and/or battery)
Time Frame
From date of randomization until six and twelve months later
Title
Device dislocation
Description
Number of device dislocations (lead and/or battery)
Time Frame
From date of randomization until six and twelve months later
Title
Lead fractures
Description
Number of lead fractures/breakages
Time Frame
From date of randomization until six and twelve months later
Title
Lead failure
Description
Number of lead failures
Time Frame
From date of randomization until six and twelve months later
Title
Battery End of Life (EOL)
Description
Number of battery End of Life (EOL)
Time Frame
From date of randomization until six and twelve months later

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Inge Wijnbergen, MD, PhD
Phone
0031402397000
Email
inge.wijnbergen@catharinaziekenhuis.nl
Facility Information:
Facility Name
Catharina Hospital
City
Eindhoven
State/Province
Noord Brabant
ZIP/Postal Code
5623EJ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabienne E Vervaat, MD
Phone
0031402397000
Email
fabienne.vervaat@catharinaziekenhuis.nl

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Efficacy of Spinal Cord Stimulation in Patients With Refractory Angina Pectoris

We'll reach out to this number within 24 hrs