Rheopheresis for Raynaud's and Digital Ulcers in Systemic Sclerosis

NCT ID: NCT05204784

Last Updated: 2022-03-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-28

Study Completion Date

2024-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Systemic Sclerosis Raynaud Phenomenon Digital Ulcer Scleroderma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Arm 1

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

Group Type EXPERIMENTAL

Rheopheresis treatment

Intervention Type 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 2

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

Group Type EXPERIMENTAL

Rheopheresis treatment

Intervention Type 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.

Control Group

Standard of care treatment with intravenous iloprost

Group Type ACTIVE_COMPARATOR

Intravenous Infusion

Intervention Type 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

Interventions

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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.

Intervention Type PROCEDURE

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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DiaMed GmbH

INDUSTRY

Sponsor Role collaborator

Peter Korsten

OTHER

Sponsor Role lead

Responsible Party

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Peter Korsten

Dr. med.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Peter Korsten, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Göttingen

Locations

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University Medical Center Göttingen

Göttingen, Lower Saxony, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Peter Korsten, Dr. med.

Role: CONTACT

+49-551-39-60400

Facility Contacts

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PETER KORSTEN

Role: primary

+49-551-39-60400

References

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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.

Reference Type BACKGROUND
PMID: 12324557 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19420368 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27189141 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26109864 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23292819 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20805294 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29318042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19629514 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28662721 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16354279 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12887730 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35382237 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27322218 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17893248 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28992170 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7506013 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24092682 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12355489 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35492333 (View on PubMed)

Other Identifiers

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36/7/21

Identifier Type: -

Identifier Source: org_study_id

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