Design and rationale of the efficacy of spinal cord stimulation in patients with refractory angina pectoris (SCRAP) trial

Abstract

Background: The use of spinal cord stimulation (SCS) in patients with refractory angina pectoris (RAP) is still under debate. Studies up to date have shown a positive effect with an improvement in quality of life. However, no double blinded randomized controlled trials have been performed.

Hypothesis & methods: The objective of this trial is to investigate if high density SCS leads to a significant reduction in the amount of myocardial ischemia in patients with RAP. Eligible patients must meet the criteria for RAP, have proven ischemia and a positive transcutaneous electrical nerve stimulator treadmill test. Patients who meet the inclusion criteria will receive an implanted spinal cord stimulator. Patients receive 6 months of high density SCS and 6 months of no stimulation using a cross-over design. The order of the treatment options is determined using randomization. The primary endpoint is the effect of SCS measured by the change in percentage of myocardial ischemia using myocardial perfusion positron emission tomography scan. Key secondary endpoints are patient related outcome measures, major cardiac adverse events and safety endpoints. The follow-up period is 1 year for the primary and key secondary endpoints.

Results: The SCRAP trial began enrollment on December 21, 2021 and is set to complete the primary assessments in June 2025. To date, January 2, 2023, 18 patients have been enrolled in the study and 3 patients have completed the 1-year follow-up.

Conclusions: The SCRAP trial is an investigator-initiated, single-center, double-blind, placebo-controlled, and cross-over randomized controlled trial investigating the efficacy of SCS in patients with RAP. (ClinicalTrials. gov Identifier: NCT04915157).

Keywords: refractory angina pectoris; spinal cord stimulation; trial design.

Figure 1

Flowchart of the screening process for inclusion into the SCRAP trial; patients eligible for participation in the SCRAP trial. A standardized TENS treadmill test is performed. Patients with a dubious standardized TENS treadmill test will be included if they have a positive result after 2 weeks of ambulatory TENS. Patients with a positive standardized TENS treadmill test will undergo a cardiac PET. CCS, canadian cardiovascular society; FFR, fractional flow reserve; MIBI‐SPECT, methoxyisobutylisonitrile single photon emission computed tomography; MRI,  magnetic resonance imaging; NRS, numeric rating scale; PET, positron emission tomography; RAND‐36, RAND 36‐item Health Survey; SAQ, seattle angina questionnaire; TENS, transcutaneous electrical nerve stimulation.

Figure 2

Flowchart of randomization process and study design; after informed consent is given a SCS is implanted. Patients are randomized into arm A or B with 6 months of spinal cord stimulation and 6 months of no stimulation or vice versa. At 6 and 12 months measurements (including PET, 6‐MWT, SAQ, NRS, CCS, and RAND‐36) are performed. The study period is 12 months. 6‐MWT, 6 min walking test; NRS, numeric rat; PET, positron emission tomography, RAND‐36, RAND 36‐item Health Survey; SCS, spinal cord stimulator.