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

Purpose

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

Condition	Intervention	Phase
Thrombotic Thrombocytopenic Purpura	Drug: Cyclosporine Drug: Prednisone	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

Genetics Home Reference related topics: factor V Leiden thrombophilia prothrombin thrombophilia thrombotic thrombocytopenic purpura

MedlinePlus related topics: Steroids

Drug Information available for: Prednisone Cyclosporine

U.S. FDA Resources

Further study details as provided by Ohio State University:

Primary Outcome Measures:

To determine if CSA given individually as an adjunct to PE decreases the frequency of exacerbation in patients with TTP compared to those patients given corticosteroids as an adjunct to PE. [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To compare the CSA and PE-treated patients to the corticosteroid and PE-treated patients in terms of the number of exchange procedures to achieve clinical remission and the relapse rate after tapering the adjuvant immune-based therapy. [ Time Frame: 2-5 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	62
Study Start Date:	November 2007
Estimated Study Completion Date:	November 2015
Estimated Primary Completion Date:	November 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Patients in this arm will receive cyclosporine (Neoral) at a dose of 2-3 mg/kg orally as an adjunct to plasma exchange.	Drug: Cyclosporine 2-3 mg/kg orally in a twice day divided dose for 6 months Other Name: Neoral
Active Comparator: 2 Patients in this arm will receive prednisone at a dose of 1 mg/kg as an adjunct to plasma exchange.	Drug: Prednisone 1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00713193

Contacts

Contact: Spero R Cataland, MD	614-293-2887	spero.cataland@osumc.edu
Contact: Haifeng M Wu, MD	614-292-9335	haifeng.wu@osumc.edu

Locations

United States, Ohio
Ohio State University	Recruiting
Columbus, Ohio, United States, 43210
Contact: Leslie Witkoff, RN 614-293-8183 leslie.witkoff@osumc.edu
Principal Investigator: Spero R Cataland, MD

Sponsors and Collaborators

Ohio State University

Investigators

Principal Investigator:

Spero R Cataland, MD

Ohio State University

More Information

No publications provided

Responsible Party:	Spero Cataland, Associate Professor of Internal Medicine, Ohio State University
ClinicalTrials.gov Identifier:	NCT00713193 History of Changes
Other Study ID Numbers:	2007H0194
Study First Received:	July 9, 2008
Last Updated:	February 13, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Ohio State University:

Idiopathic TTP
Treatment
Exacerbation
Relapse
Plasma Exchange

Additional relevant MeSH terms:

Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Thrombosis
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Thrombophilia

Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Cyclosporins
Cyclosporine
Prednisone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 22, 2013