Rheopheresis for Raynaud's and Digital Ulcers in Systemic Sclerosis

NCT05204784 | Unknown

• 1 other identifier: 36/7/21
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Systemic Sclerosis; Raynaud Phenomenon; Digital Ulcer; Scleroderma

Keywords

Rheopheresis; Raynaud Phenomenon; Systemic Sclerosis; Digital Ulcers; Therapeutic plasma exchange

Outcome Measures

Primary Outcomes (1)

• Raynaud Condition Score (RCS)

  changes of the Raynaud Condition after treatment, higher RCS denotes worse clinical findings

  24 weeks

Secondary Outcomes (7)

• Development of new digital ulcers

  24 weeks

• Time to healing of existing digital ulcers

  24 weeks

• Scleroderma Health Assessment Questionnaire

  24 weeks

• Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score

  24 weeks

• Quick DASH

  24 weeks

Other Outcomes (1)

• Exploratory objectives

  24 weeks

Study Arms (3)

Arm 1

EXPERIMENTAL

2 Rheopheresis treatments per week x 2, followed by 8 weeks without treatment, 8 overall treatments

Procedure: Rheopheresis treatment

Arm 2

EXPERIMENTAL

2 Rheopheresis treatments in week 1, followed by 1 treatment every 2 weeks, 8 overall treatments

Procedure: Rheopheresis treatment

Control Group

ACTIVE COMPARATOR

Standard of care treatment with intravenous iloprost

Drug: Intravenous Infusion

Interventions

Rheopheresis treatment PROCEDURE

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.

Arm 1; Arm 2

Intravenous Infusion DRUG

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

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients fulfilling ACR/EULAR classification criteria for SSc
• Presence of RP with or without DU
• Failure of at least one standard of care treatment (CCB or iloprost) for at least three months
• RCS \> 4
• Possibility to obtain venous access (either through a peripherally or centrally inserted catheter)

You may not qualify if:

• Significant anemia (\<8 g/dL)
• Clinically relevant hemorrhagic diathesis or coagulopathy
• Diabetes mellitus
• Serious acute or chronic kidney (eGFR\<30 ml/min/1.73m2) or liver failure
• Hypotension with systolic blood pressure \<100 mmHg
• Chronic viral infections (HIV, Hepatitis B, C)
• Epilepsia, psychosis, dementia, or other relevant neurologic condition precluding the conduct of plasmapheresis
• Malignant disease or any other condition with life expectancy \<12 months
• Known history of alcohol or drug abuse
• Long-term serious tobacco abuse with documented severe vascular disease (Fontaine \>III).
• Severe hyperlipoproteinemia, defined as a significant elevation of Lp(a) or LDL cholesterol despite standard doses of medical therapy

Sponsors & Collaborators

• Peter Korsten: lead
• DiaMed GmbH: collaborator

Study Sites (1)

University Medical Center Göttingen

Göttingen, Lower Saxony, 37075, Germany

RECRUITING

Related Publications (19)

• Wigley FM. Clinical practice. Raynaud's Phenomenon. N Engl J Med. 2002 Sep 26;347(13):1001-8. doi: 10.1056/NEJMcp013013. No abstract available.

  PMID: 12324557 BACKGROUND

• Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009 May 7;360(19):1989-2003. doi: 10.1056/NEJMra0806188. No abstract available.

  PMID: 19420368 BACKGROUND

• 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.

  PMID: 27189141 BACKGROUND

• 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.

  PMID: 26109864 BACKGROUND

• 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.

  PMID: 23292819 BACKGROUND

• 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.

  PMID: 20805294 BACKGROUND

• 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.

  PMID: 29318042 BACKGROUND

• 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.

  PMID: 19629514 BACKGROUND

• Kostal M, Drsata J, Blaha M, Lanska 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.

  PMID: 28662721 BACKGROUND

• 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. doi: 10.1111/j.1744-9987.2005.00276.x.

  PMID: 16354279 BACKGROUND

• Klingel R, Mumme C, Fassbender T, Himmelsbach F, Altes U, Lotz J, Pohlmann T, Beyer J, Kustner 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. doi: 10.1046/j.1526-0968.2003.00082.x.

  PMID: 12887730 BACKGROUND

• Harris ES, Meiselman HJ, Moriarty PM, Metzger A, Malkovsky M. Therapeutic plasma exchange for the treatment of systemic sclerosis: A comprehensive review and analysis. J Scleroderma Relat Disord. 2018 Jun;3(2):132-152. doi: 10.1177/2397198318758606. Epub 2018 Mar 9.

  PMID: 35382237 BACKGROUND

• 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.

  PMID: 27322218 BACKGROUND

• 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. doi: 10.1136/ard.2007.078923. Epub 2007 Sep 24.

  PMID: 17893248 BACKGROUND

• 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.

  PMID: 28992170 BACKGROUND

• 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. doi: 10.7326/0003-4819-120-3-199402010-00004.

  PMID: 7506013 BACKGROUND

• 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, Muller-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.

  PMID: 24092682 BACKGROUND

• 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, Jimenez 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. doi: 10.1002/art.10486.

  PMID: 12355489 BACKGROUND

• Rademacher JG, Tampe B, Borisch A, Buschfort RM, von Figura A, Asendorf T, Korsten P. Study Protocol: A Randomized Controlled Prospective Single-Center Feasibility Study of Rheopheresis for Raynaud's Syndrome and Digital Ulcers in Systemic Sclerosis (RHEACT Study). Front Med (Lausanne). 2022 Apr 14;9:871744. doi: 10.3389/fmed.2022.871744. eCollection 2022.

  PMID: 35492333 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; Raynaud Disease; digital ulcers; Scleroderma, Diffuse

Interventions

Infusions, Intravenous

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular

Intervention Hierarchy (Ancestors)

Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Study Officials

• Peter Korsten, Dr. med.

  University Medical Center Göttingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Korsten, Dr. med.

CONTACT

+49-551-39-60400; peter.korsten@med.uni-goettingen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. med.

Study Record Dates

• First Submitted: November 29, 2021
• First Posted: January 24, 2022
• Study Start: February 28, 2022
• Primary Completion: December 1, 2023
• Study Completion: June 1, 2024
• Last Updated: March 23, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)