Thrombotic Thrombocytopenic PurpuraPhase 3NCT00713193
Study of Cyclosporine or Corticosteroids as an Adjunct to Plasma Exchange in Thrombotic Thrombocytopenic Purpura (TTP)
A Phase 3 study testing Cyclosporine and Prednisone in people with Thrombotic Thrombocytopenic Purpura, run by Ohio State University at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thrombotic Thrombocytopenic Purpura
- What is being tested?
- Cyclosporine and Prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to 20 Sep 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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
Read the 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.
- Conditions
- Thrombotic Thrombocytopenic Purpura
- Being tested
- Cyclosporine, Prednisone
- Keywords
- Idiopathic TTP, Treatment, Exacerbation, Relapse, Plasma Exchange
- Medical subject headings
- Purpura, Thrombotic Thrombocytopenic, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclosporineDrug
Also called Neoral
2-3 mg/kg orally in a twice day divided dose for 6 months
PrednisoneDrug
Also called Steroid arm
1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Days to achieve a clinical response, defined as a normal platelet count (>150 x 109/L), normal LDH, and no new end organ injury.
Measured: Time to starting treatment until 6 months after the last PEX procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2008 (estimated)
- Study startNov 2007
- Primary completion20 Sep 2017
- Study completion20 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thrombotic Thrombocytopenic PurpuraStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Principal investigator, Spero Cataland, Ohio State University
- Investigators
- Spero R Cataland, MD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00713193
- Sponsor's protocol ID
- 2007H0194
- Other IDs
- R01FD003932
- Status last verified
- Apr 2023
- First submitted
- 9 Jul 2008
- Last updated
- 3 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: data being evaluated and reviewed, manuscript in preparation for final report to FDA
Publications
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.
PubMed 29296854
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00713193
- Acronym / sponsor ID
- 2007H0194
- Conditions
- Thrombotic Thrombocytopenic Purpura
- Keywords
- Idiopathic TTP, Treatment, Exacerbation, Relapse, Plasma Exchange
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- Nov 2007
- Primary completion
- 20 Sep 2017 (actual)
- Study completion
- 20 Sep 2017 (actual)
- First posted
- 11 Jul 2008 (estimated)
- Results
- Posted 28 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclosporine and Plasma Exchange Arm | Experimental | Drug: CyclosporinePatients 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. |
| Prednisone and Plasma Exchange Arm | Active comparator | Drug: PrednisonePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CyclosporineAlso: Neoral2-3 mg/kg orally in a twice day divided dose for 6 months | Drug | Cyclosporine and Plasma Exchange Arm |
| PrednisoneAlso: Steroid arm1 mg/kg orally, daily for at least 30 days, then tapered over 30 days after achieving remission. | Drug | Prednisone and Plasma Exchange Arm |
Primary outcome
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
Number of Participants with Exacerbations in the CSA/PEX Arm Compared to the Steroids/PEX Arm
1 secondary outcome
Time in Days to Achieve a Clinical Response, Comparing the CSA/PEX Arm to the Steroids/PEX Arm.
Time frame: Time to starting treatment until 6 months after the last PEX procedure
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29296854Cataland 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.
- Individual participant dataSharing planned: Yes. data being evaluated and reviewed, manuscript in preparation for final report to FDA
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Spero R Cataland, MD principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclosporine and Prednisone in people with Thrombotic Thrombocytopenic Purpura, run by Ohio State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00713193, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.