Thrombotic Thrombocytopenic Purpura
Conditions
Keywords
Idiopathic TTP, Treatment, Exacerbation, Relapse, Plasma Exchange
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.
Interventions
DRUGCyclosporine
2-3 mg/kg orally in a twice day divided dose for 6 months
DRUGPrednisone
1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission.
Sponsors
Food and Drug Administration (FDA)
Ohio State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Number of Participants with Exacerbations in the CSA/PEX Arm Compared to the Steroids/PEX Arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Days to achieve a clinical response, defined as a normal platelet count (\>150 x 109/L), normal LDH, and no new end organ injury. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 12 |
| 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. | 14 |
| Total | 26 |
Baseline characteristics
| Characteristic | CSA Arm | Prednisone Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 14 Participants | 26 Participants |
| Age, Continuous | 40 years | 37 years | 37 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 14 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 14 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 0 Participants | 10 Participants |
| Region of Enrollment United States | 12 participants | 14 participants | 26 participants |
| Sex: Female, Male Female | 2 Participants | 14 Participants | 16 Participants |
| Sex: Female, Male Male | 10 Participants | 0 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 12 | 1 / 14 |
| other Total, other adverse events | 0 / 12 | 0 / 14 |
| serious Total, serious adverse events | 0 / 12 | 0 / 14 |
Outcome results
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
Time frame: From the start of treatment until 30 days after discharge from the last PEX procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSA Arm | Number of Participants With Exacerbations in the CSA/PEX Arm Compared to the Steroids/PEX Arm | 3 participants |
| Prednisone Arm | Number of Participants With Exacerbations in the CSA/PEX Arm Compared to the Steroids/PEX Arm | 1 participants |
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.
Time frame: Time to starting treatment until 6 months after the last PEX procedure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CSA Arm | Time in Days to Achieve a Clinical Response, Comparing the CSA/PEX Arm to the Steroids/PEX Arm. | 5 Days |
| Prednisone Arm | Time in Days to Achieve a Clinical Response, Comparing the CSA/PEX Arm to the Steroids/PEX Arm. | 5 Days |