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

Primary Purpose

Thrombotic Thrombocytopenic Purpura

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Cyclosporine
Prednisone
Sponsored by
Ohio State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thrombotic Thrombocytopenic Purpura focused on measuring Idiopathic TTP, Treatment, Exacerbation, Relapse, Plasma Exchange

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Sites / Locations

  • Ohio State University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cyclosporine and Plasma Exchange Arm

Prednisone and Plasma Exchange Arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Time in Days to Achieve a Clinical Response, Comparing the CSA/PEX Arm to the Steroids/PEX Arm.
Days to achieve a clinical response, defined as a normal platelet count (>150 x 109/L), normal LDH, and no new end organ injury.

Full Information

First Posted
July 9, 2008
Last Updated
April 29, 2023
Sponsor
Ohio State University
Collaborators
Food and Drug Administration (FDA)
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1. Study Identification

Unique Protocol Identification Number
NCT00713193
Brief Title
Study of Cyclosporine or Corticosteroids as an Adjunct to Plasma Exchange in Thrombotic Thrombocytopenic Purpura (TTP)
Official Title
A Multi-Center, Randomized Study of Cyclosporine or Corticosteroids as an Adjunct to Plasma Exchange in the Initial Therapy of Thrombotic Thrombocytopenic Purpura (TTP)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
September 20, 2017 (Actual)
Study Completion Date
September 20, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University
Collaborators
Food and Drug Administration (FDA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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
Detailed Description
TTP is a rare blood disorder that causes blood clots to form in the small blood vessels throughout the body, including the kidneys, brain, abdomen, and the heart. Plasma exchange is the standard treatment for TTP. Plasma exchange is a treatment that removes the plasma (the liquid portion of the blood without any cells) from a patient and replaces it with plasma from a donor. With plasma exchange, 90% of patients achieve a remission of the disease. Unfortunately, up to one half of patient will relapse after the plasma exchange has stopped, leading to significant complications and added risks to the patient. This study randomizes patients to receive either prednisone or cyclosporine as an adjunct to plasma exchange, with the cyclosporine arm being the experimental arm of the study. All patients will undergo plasma exchange but will be randomized to receive either prednisone or cyclosporine as an adjunct to plasma exchange. Previous studies suggested that cyclosporine was superior to prednisone as an adjunct to plasma exchange, and therefore this randomized study attempts to confirm the findings of two previous single institution studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Thrombocytopenic Purpura
Keywords
Idiopathic TTP, Treatment, Exacerbation, Relapse, Plasma Exchange

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cyclosporine and Plasma Exchange Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Prednisone and Plasma Exchange Arm
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Other Intervention Name(s)
Neoral
Intervention Description
2-3 mg/kg orally in a twice day divided dose for 6 months
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Steroid arm
Intervention Description
1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission.
Primary Outcome Measure Information:
Title
Number of Participants With Exacerbations in the CSA/PEX Arm Compared to the Steroids/PEX Arm
Description
Number of Participants with Exacerbations in the CSA/PEX Arm Compared to the Steroids/PEX Arm
Time Frame
From the start of treatment until 30 days after discharge from the last PEX procedure
Secondary Outcome Measure Information:
Title
Time in Days to Achieve a Clinical Response, Comparing the CSA/PEX Arm to the Steroids/PEX Arm.
Description
Days to achieve a clinical response, defined as a normal platelet count (>150 x 109/L), normal LDH, and no new end organ injury.
Time Frame
Time to starting treatment until 6 months after the last PEX procedure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Spero R Cataland, MD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
data being evaluated and reviewed, manuscript in preparation for final report to FDA
IPD Sharing Time Frame
Presently available to share
IPD Sharing Access Criteria
Request needs to be made to investigators
Citations:
PubMed Identifier
29296854
Citation
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.
Results Reference
derived

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

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