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| ID | Type | Description | Link |
|---|---|---|---|
| R01FD003932 | U.S. FDA Grant/Contract | View source |
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| Name | Class |
|---|---|
| Food and Drug Administration (FDA) | FED |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclosporine | Drug | 2-3 mg/kg orally in a twice day divided dose for 6 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Time to starting treatment until 6 months after the last PEX procedure |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Spero R Cataland, MD | Ohio State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ohio State University | Columbus | Ohio | 43210 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29296854 | Derived | 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. |
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data being evaluated and reviewed, manuscript in preparation for final report to FDA
Presently available to share
Request needs to be made to investigators
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| ID | Title | Description |
|---|---|---|
| FG000 | CSA Arm | Patients in this arm will receive cyclosporine (Neoral) at a dose of 2-3 mg/kg orally as an adjunct to plasma exchange. Cyclosporine: 2-3 mg/kg orally in a twice day divided dose for 6 months 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. 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. |
| FG001 | Prednisone Arm | Patients in this arm will receive prednisone at a dose of 1 mg/kg as an adjunct to plasma exchange. Prednisone: 1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission. 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. 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | CSA Arm | Patients in this arm will receive cyclosporine (Neoral) at a dose of 2-3 mg/kg orally as an adjunct to plasma exchange. At the time of diagnosis, patients will be started on daily cyclosporine (Neoral) therapy at a dose of 2-3 mg/kg/day (rounded to the nearest 50 mg increment) concurrent with daily plasma exchange. Doses will be administered in the capsule form. The total dose will be divided into twice daily dosing. For consistency and standardization of cyclosporine levels throughout the study, doses of Neoral (cyclosporine) should be given at 8 AM and 8 PM each day. Neoral (cyclosporine) should be taken on an empty stomach, and patients should not eat for at least 30 minutes after their dose of Neoral (cyclosporine). Cyclosporine will be continued for a total of six months of therapy and then discontinued. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Posted | Number | participants | From the start of treatment until 30 days after discharge from the last PEX procedure |
|
Adverse events data were collected over the first 6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CSA Arm | 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. Cyclosporine: 2-3 mg/kg orally in a twice day divided dose for 6 months |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Spero R Cataland | Ohio State University | 6142939441 | spero.cataland@osumc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 3, 2011 | Oct 1, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011697 | Purpura, Thrombotic Thrombocytopenic |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D011696 | Purpura, Thrombocytopenic |
| D011693 | Purpura |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D016572 | Cyclosporine |
| D011241 | Prednisone |
| ID | Term |
|---|---|
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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| Prednisone | Drug | 1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission. |
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| BG001 | Prednisone Arm | Patients in this arm will receive prednisone at a dose of 1 mg/kg as an adjunct to plasma exchange. Prednisone: 1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission. At the time of diagnosis, patients will be started on daily prednisone therapy at a dose of 1 mg/kg/day (rounded off to the nearest 20 mg multiple) concurrently with daily PE. Patients unable to take oral corticosteroids will be switched to an equivalent intravenous corticosteroid until they are able to take oral medications. Patients may receive intravenous corticosteroids at any time to urgently treat reactions to the infused plasma and for prophylaxis against future reactions prior to the next TPE. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG001 | Prednisone Arm | 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. Prednisone: 1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission. |
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|
| Secondary | 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. | Posted | Median | Full Range | Days | Time to starting treatment until 6 months after the last PEX procedure |
|
|
|
| 1 |
| 12 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Prednisone Arm | 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. Prednisone: 1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission. | 1 | 14 | 0 | 14 | 0 | 14 |
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| D006425 |
| Hemic and Lymphatic Diseases |
| D057049 | Thrombotic Microangiopathies |
| D013921 | Thrombocytopenia |
| D001791 | Blood Platelet Disorders |
| D000095542 | Cytopenia |
| D019851 | Thrombophilia |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
| D020969 | Disease Attributes |
| D010455 |
| Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |