Study of Cyclosporine or Corticosteroids as an Adjunct to Plasma Exchange in Thrombotic Thrombocytopenic Purpura (TTP)

NCT00713193 | Completed Phase 3 Results DMC

• 2 other identifiers: 2007H0194R01FD003932
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This research involves the use of immune base therapy as an adjunct to plasma exchange, the present standard of care for thrombotic thrombocytopenic purpura (TTP). Funding source -FDA OOPD

Conditions

Thrombotic Thrombocytopenic Purpura

Keywords

Idiopathic TTP; Treatment; Exacerbation; Relapse; Plasma Exchange

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Exacerbations in the CSA/PEX Arm Compared to the Steroids/PEX Arm

  Number of Participants with Exacerbations in the CSA/PEX Arm Compared to the Steroids/PEX Arm

  From the start of treatment until 30 days after discharge from the last PEX procedure

Secondary Outcomes (1)

• Time in Days to Achieve a Clinical Response, Comparing the CSA/PEX Arm to the Steroids/PEX Arm.

  Time to starting treatment until 6 months after the last PEX procedure

Study Arms (2)

Cyclosporine and Plasma Exchange Arm

EXPERIMENTAL

Patients in this arm will receive cyclosporine (Neoral) at a dose of 2-3 mg/kg orally as an adjunct to plasma exchange. All patients initiated daily PEX (one plasma volume), using plasma as the replacement fluid. Patients randomized to the CSA arm received CSA at a dose of 2-3 mg/kg (rounded to the nearest 50 mg increment) divided into a twice daily dosing (Figure 1a). Patients randomized to CSA did not receive steroids, but were permitted to receive hydrocortisone as required for any hypersensitivity reactions to the infused plasma. Daily PEX was continued until a clinical response was achieved, then patients received PEX every other day for 2 additional procedures, with the first day that the platelet count and LDH were normal counting as the first of the 2 procedures.

Drug: Cyclosporine

Prednisone and Plasma Exchange Arm

ACTIVE COMPARATOR

Patients in this arm will receive prednisone at a dose of 1 mg/kg as an adjunct to plasma exchange. All patients initiated daily PEX (one plasma volume), using plasma as the replacement fluid. Patients randomized to the corticosteroid arm received prednisone at a dose of 1 mg/kg/d rounded to the nearest 20 mg increment. Daily PEX was continued until a clinical response was achieved, then patients received PEX every other day for 2 additional procedures, with the first day that the platelet count and LDH were normal counting as the first of the 2 procedures.

Drug: Prednisone

Interventions

Cyclosporine DRUG

2-3 mg/kg orally in a twice day divided dose for 6 months

Also known as: Neoral

Cyclosporine and Plasma Exchange Arm

Prednisone DRUG

1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission.

Also known as: Steroid arm

Prednisone and Plasma Exchange Arm

Eligibility Criteria

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

You may qualify if:

• Patients with a clinical diagnosis of idiopathic TTP as defined by a microangiopathic hemolytic anemia and thrombocytopenia (\<100 x 103)
• Additional components of the pentad (fever, renal and neurologic abnormalities) need not be present.
• Additional explanations for the microangiopathic changes including DIC and malignancy should be excluded.
• Patients with pregnancy associated TTP will be permitted on this therapeutic trial if the child is delivered prior to the initiation of therapy for TTP. However, female patients that are breastfeeding and are unwilling to discontinue breastfeeding at the time of enrollment will be excluded from this study
• Patients with a previous diagnosis of TTP are eligible to be enrolled provided they meet eligibility criteria and have not been treated for an TTP in the past 30 days
• Given the potential for nephrotoxicity with CSA, all patients must have a serum creatinine of \< 2.5 mg/dl prior to enrollment

You may not qualify if:

• In light of concern for the prompt initiation of PE, all patients with suspected TTP may be enrolled on this trial. If it is subsequently found that the patient does not meet enrollment criteria, they will be removed and their spot replaced for study purposes. Patients removed from the study after enrollment will continue to be followed longitudinally for 6 months to be monitored for safety and will be included in the safety database.
• Patients with TTP clinically categorized as secondary to stem cell transplant and solid organ, bloody diarrhea associated, malignancy associated, and drug associated will not be enrolled on this therapeutic study.
• Incarcerated patients will be excluded from the study due to the inherent difficulties in maintaining close follow-up for study purposes in patients who are incarcerated.
• Any patients already being treated chronically with corticosteroids or cyclosporine and taking these at the time of their presentation will be excluded from this study.
• Female patients that are breastfeeding and are unwilling to discontinue breastfeeding at the time of enrollment will be excluded from this study
• Patients taking any medications contraindicated in combination with CSA that cannot be safely discontinued will be excluded from this study.

Sponsors & Collaborators

• Ohio State University: lead
• Food and Drug Administration (FDA): collaborator

Study Sites (1)

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Cataland SR, Kourlas PJ, Yang S, Geyer S, Witkoff L, Wu H, Masias C, George JN, Wu HM. Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura. Blood Adv. 2017 Oct 23;1(23):2075-2082. doi: 10.1182/bloodadvances.2017009308. eCollection 2017 Oct 24.

  PMID: 29296854 DERIVED

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic; Recurrence

Interventions

Cyclosporine; Prednisone

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Spero R Cataland
• Organization: Ohio State University

spero.cataland@osumc.edu

6142939441

Study Officials

• Spero R Cataland, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Internal Medicine

Study Record Dates

• First Submitted: July 9, 2008
• First Posted: July 11, 2008
• Study Start: November 1, 2007
• Primary Completion: September 20, 2017
• Study Completion: September 20, 2017
• Last Updated: May 3, 2023
• Results First Posted: April 28, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Presently available to share
• Access Criteria: Request needs to be made to investigators

Locations

US (1)