Study Protocol: A Randomized Controlled Prospective Single-Center Feasibility Study of Rheopheresis for Raynaud's Syndrome and Digital Ulcers in Systemic Sclerosis (RHEACT Study)

Abstract

Introduction: Raynaud's phenomenon (RP) and digital ulcers (DU) are frequent manifestations of Systemic Sclerosis (SSc). Despite being very common in SSc patients, both conditions have proven to be notoriously difficult to study. There are very few available approved drugs with varying efficacy. It has been shown that the presence of DU is associated with increased whole blood viscosity (WBV). Rheopheresis (RheoP) is an extracorporeal apheresis technique used to treat microcirculatory disorders by improving blood viscosity. Improved blood flow and wound healing after RheoP treatments have been reported in single case reports.

Methods and analysis: We report the clinical trial protocol of "A randomized controlled prospective single-center feasibility study of Rheopheresis for Raynaud's syndrome and Digital Ulcers in Systemic Sclerosis (RHEACT)." RHEACT aims to investigate the efficacy of RheoP on the Raynaud Condition Score (RCS) as the primary efficacy outcome measure after 16 weeks from baseline. Thirty patients will be randomized in a 1:1:1 ratio to one of two RheoP treatment groups or assigned to the standard of care (SoC) control group (intravenous iloprost). Secondary endpoints include changes in DU, changes in nailfold video capillaroscopy and patient-reported-outcomes (Scleroderma Health Assessment Questionnaire, FACIT-Fatigue, and the Disability of Arm, Shoulder, and Hand, quick version).

Discussion: Apheresis techniques have been investigated in SSc but mainly in observational, retrospective studies, or single case reports. RheoP is a pathophysiologically driven potential new therapy for heavily burdened patients with SSc-associated secondary RP with or without DU.

Ethics and dissemination: The study was registered at clinicaltrials.gov (Identifier: NCT05204784). Furthermore, the study is made publicly available on the website of the German network of Systemic Sclerosis "Deutsches Netzwerk Systemische Sklerodermie (DNSS)."

Keywords: Raynaud’s phenomenon; blood viscosity; digital ulcers; rheopheresis; systemic sclerosis; therapeutic plasma exchange.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Rademacher, Tampe, Borisch, Buschfort, von Figura, Asendorf and Korsten.

Figures

FIGURE 1

Schematic of the rheopheresis procedure. After obtaining venous access, anticoagulated blood is pumped through a plasma filter. The plasma is then run through the rheofilter, and large plasma proteins are removed. Finally, cells are reinfused, and blood is returned to the patient. The figure was created with biorender.com.

FIGURE 2

Study design. Treatment schedule (red arrows or blocks) and intervention and control groups assessments. The figure was created with biorender.com. BSL, baseline; SCR, screening; V, visit.