Rheopheresis for Raynaud's and Digital Ulcers in Systemic Sclerosis

Systemic Sclerosis Clinical Trial

— RHEACT  

Official title:

A Randomized Controlled Prospective Single-center Feasibility Study of Rheopheresis for Raynaud's Syndrome and Digital Ulcers in Systemic Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05204784
• Other study ID #: 36/7/21
• Status: Recruiting
• Phase: N/A
• Start date: February 28, 2022
• Est. completion date: June 2024

Study information

• Verified date: March 2022
• Source: University of Göttingen
• Contact: Peter Korsten, Dr. med.
• Phone: +49-551-39-60400
• Email: peter.korsten[@]med.uni-goettingen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this feasibility study, we aim to explore therapeutic Rheopheresis (RheoP) as a novel treatment option for SSc-associated Raynaud's phenomenon and/or digital ulcers and compare it to the standard of care treatment (intravenous iloprost. RheoP has been used for RP/DU with some success in observational studies, nevertheless, the optimal treatment modality, duration, or frequency of RheoP (and PEX in general) in SSc has not been established as of yet.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult patients fulfilling ACR/EULAR classification criteria for SSc

2. Presence of RP with or without DU

3. Failure of at least one standard of care treatment (CCB or iloprost) for at least three months

4. RCS > 4

5. Possibility to obtain venous access (either through a peripherally or centrally inserted catheter)

Exclusion Criteria:

1. Significant anemia (<8 g/dL)

2. Clinically relevant hemorrhagic diathesis or coagulopathy

3. Diabetes mellitus

4. Serious acute or chronic kidney (eGFR<30 ml/min/1.73m2) or liver failure

5. Hypotension with systolic blood pressure <100 mmHg

6. Chronic viral infections (HIV, Hepatitis B, C)

7. Epilepsia, psychosis, dementia, or other relevant neurologic condition precluding the conduct of plasmapheresis

8. Malignant disease or any other condition with life expectancy <12 months

9. Known history of alcohol or drug abuse

10. Long-term serious tobacco abuse with documented severe vascular disease (Fontaine >III).

11. Severe hyperlipoproteinemia, defined as a significant elevation of Lp(a) or LDL cholesterol despite standard doses of medical therapy

Related Conditions & MeSH terms

• Digital Ulcer
• Raynaud Disease
• Raynaud Phenomenon
• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Skin Ulcer
• Systemic Sclerosis
• Ulcer

Intervention

Procedure:
• Rheopheresis treatment
After obtaining venous access, anticoagulated blood is pumped through a plasmafilter. 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.

Drug:
• Intravenous Infusion
Standard of care treatment consists of intravenous iloprost infusions at a dose of 0.5-2 ng/kg/min administered over at least 6 hours as per local standard

Locations

Country	Name	City	State
Germany	University Medical Center Göttingen	Göttingen	Lower Saxony

Sponsors (2)

Lead Sponsor	Collaborator
Peter Korsten	DiaMed GmbH

Country where clinical trial is conducted

Germany, 

References & Publications (18)

Abraham S, Steen V. Optimal management of digital ulcers in systemic sclerosis. Ther Clin Risk Manag. 2015 Jun 15;11:939-47. doi: 10.2147/TCRM.S82561. eCollection 2015. Review. — View Citation

Allanore Y, Simms R, Distler O, Trojanowska M, Pope J, Denton CP, Varga J. Systemic sclerosis. Nat Rev Dis Primers. 2015 Apr 23;1:15002. doi: 10.1038/nrdp.2015.2. Review. — View Citation

Cutolo M, Smith V, Furst DE, Khanna D, Herrick AL. Points to consider-Raynaud's phenomenon in systemic sclerosis. Rheumatology (Oxford). 2017 Sep 1;56(suppl_5):v45-v48. doi: 10.1093/rheumatology/kex199. Review. — View Citation

Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009 May 7;360(19):1989-2003. doi: 10.1056/NEJMra0806188. Review. — View Citation

Harris ES, Meiselman HJ, Moriarty PM, Metzger A, Malkovsky M. Therapeutic plasma exchange for the treatment of systemic sclerosis: A comprehensive review and analysis. Journal of Scleroderma and Related Disorders- 2018; 3(2): 132-152.

Herrick AL. Management of Raynaud's phenomenon and digital ischemia. Curr Rheumatol Rep. 2013 Jan;15(1):303. doi: 10.1007/s11926-012-0303-1. Review. — View Citation

Khanna D, Lovell DJ, Giannini E, Clements PJ, Merkel PA, Seibold JR, Matucci-Cerinic M, Denton CP, Mayes MD, Steen VD, Varga J, Furst DE; Scleroderma Clinical Trials Consortium co-authors. Development of a provisional core set of response measures for clinical trials of systemic sclerosis. Ann Rheum Dis. 2008 May;67(5):703-9. Epub 2007 Sep 24. — View Citation

Klingel R, Erdtracht B, Gauss V, Piazolo A, Mausfeld-Lafdhiya P, Diehm C. Rheopheresis in patients with critical limb ischemia--results of an open label prospective pilot trial. Ther Apher Dial. 2005 Dec;9(6):473-81. — View Citation

Klingel R, Mumme C, Fassbender T, Himmelsbach F, Altes U, Lotz J, Pohlmann T, Beyer J, Küstner E. Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open label prospective pilot trial. Ther Apher Dial. 2003 Aug;7(4):444-55. — View Citation

Korsten P, Niewold TB, Zeisberg M, Utset TO, Cho D, Zachary LS, Sweiss NJ, Volkov S. Increased Whole Blood Viscosity Is Associated with the Presence of Digital Ulcers in Systemic Sclerosis: Results from a Cross-Sectional Pilot Study. Autoimmune Dis. 2017;2017:3529214. doi: 10.1155/2017/3529214. Epub 2017 Nov 29. — View Citation

Koss MJ, Kurz P, Tsobanelis T, Lehmacher W, Fassbender C, Klingel R, Koch FH. Prospective, randomized, controlled clinical study evaluating the efficacy of Rheopheresis for dry age-related macular degeneration. Dry AMD treatment with Rheopheresis Trial-ART. Graefes Arch Clin Exp Ophthalmol. 2009 Oct;247(10):1297-306. doi: 10.1007/s00417-009-1113-7. Epub 2009 Jul 23. — View Citation

Kostal M, Drsata J, Bláha M, Lánská M, Chrobok V. Rheopheresis in treatment of idiopathic sensorineural sudden hearing loss. J Otolaryngol Head Neck Surg. 2017 Jun 29;46(1):50. doi: 10.1186/s40463-017-0228-9. — View Citation

Matucci-Cerinic M, Denton CP, Furst DE, Mayes MD, Hsu VM, Carpentier P, Wigley FM, Black CM, Fessler BJ, Merkel PA, Pope JE, Sweiss NJ, Doyle MK, Hellmich B, Medsger TA Jr, Morganti A, Kramer F, Korn JH, Seibold JR. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2011 Jan;70(1):32-8. doi: 10.1136/ard.2010.130658. Epub 2010 Aug 30. — View Citation

Merkel PA, Herlyn K, Martin RW, Anderson JJ, Mayes MD, Bell P, Korn JH, Simms RW, Csuka ME, Medsger TA Jr, Rothfield NF, Ellman MH, Collier DH, Weinstein A, Furst DE, Jiménez SA, White B, Seibold JR, Wigley FM; Scleroderma Clinical Trials Consortium. Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon. Arthritis Rheum. 2002 Sep;46(9):2410-20. — View Citation

Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, Dunbar NM, Witt V, Wu Y, Shaz BH. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J Clin Apher. 2016 Jun;31(3):149-62. doi: 10.1002/jca.21470. Review. — View Citation

van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Müller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Ellen Csuka M, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013 Nov;72(11):1747-55. doi: 10.1136/annrheumdis-2013-204424. — View Citation

Wigley FM, Wise RA, Seibold JR, McCloskey DA, Kujala G, Medsger TA Jr, Steen VD, Varga J, Jimenez S, Mayes M, Clements PJ, Weiner SR, Porter J, Ellman M, Wise C, Kaufman LD, Williams J, Dole W. Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Intern Med. 1994 Feb 1;120(3):199-206. — View Citation

Wigley FM. Clinical practice. Raynaud's Phenomenon. N Engl J Med. 2002 Sep 26;347(13):1001-8. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory objectives	changes in miRNA	24 weeks
Primary	Raynaud Condition Score (RCS)	changes of the Raynaud Condition after treatment, higher RCS denotes worse clinical findings	24 weeks
Secondary	Development of new digital ulcers	To assess the number of new digital ulcers with treatment	24 weeks
Secondary	Time to healing of existing digital ulcers	Time to healing of existing digital ulcers	24 weeks
Secondary	Scleroderma Health Assessment Questionnaire	Changes in the SHAQ with treatment; higher scores mean better functional status	24 weeks
Secondary	Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score	changes in the FACIT-Fatigue score with treatment; higher scores indicate a better clinical status	24 weeks
Secondary	Quick DASH	changes in the Quick DASH with treatment; lower scores mean better functional status	24 weeks
Secondary	Nailfold video capillaroscopy changes	changes in in NVC assessments with treatment	24 weeks
Secondary	Whole blood viscosity	changes in Whole blood viscosity with treatment	24 weeks