Thrombotic Thrombocytopenic Purpura
Conditions
Keywords
TTP, Thrombotic Thrombocytopenic Purpura
Brief summary
The purpose of the study is to find out if administration of danazol with plasma exchange and corticosteroids will reduce the number of plasma exchanges required to control Thrombotic Thrombocytopenic Purpura (TTP).
Detailed description
Danazol is a synthetic steroid hormone structurally resembling a group of natural hormones (androgens)found in the body. Danazol has immune modifying activity and is effective in treatment of blood disorders with low platelet counts such as idiopathic thrombocytopenic purpura (however FDA has not yet approved danazol for this disorder). A study of danazol in conjunction with plasma exchange for thrombotic thrombocytopenic purpura showed that danazol decreased the number of plasma exchanges required by approximately 80% and reduced the time needed to control the disease. It's not clear how danazol works in TTP. It is not approved by the FDA for the treatment of TTP.
Interventions
DRUGDanazol
Danazol 600 mg PO will be initiated with plasma exchange and corticosteroids at the time of enrollment.
Sponsors
Beth Israel Medical Center
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* TTP with platelets less than 100,000 and microangiopathic hemolytic anemia * Age greater than 18 and less than 60 * LDH \> 2x upper limit of normal * PT and PTT normal * Patients must give signed informed consent * Pre-menopausal woman must have negative pregnancy test. * TTP not related to underlying cancer, treatment of cancer or transplantation. * TTP not associated with drugs.
Exclusion criteria
* LFTs AST/ALT \> 2x upper limit of normal * Hepatitis B and Hepatitis C infection. * HIV with active opportunistic infections * Acute or chronic Disseminated Intravascular Coagulation (DIC), defined as D-dimer 8ug/ml and fibrinogen\<100 mg/dl * TTP related to drugs, malignancy and transplantation. * Pregnancy * Concurrent other investigational drug use during this study. * Porphyria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Plasma Exchanges | up to 30 days | The total number of plasma exchanges performed after initiation of the first plasma exchange. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay | up to 30 days | — |
| Number of Participants With Complete and Continuous Response Rate | At 2 Years | — |
| Time to Remission | up to 30 days | — |
| Number of Participants With Relapses | up to 12 years | Number of participants with relapses |
| Number of Relapses | up to 12 years | Number of relapses |
| Time to Relapse | up to 12 years | — |
Countries
United States
Participant flow
Recruitment details
Study opened for patient recruitment on Oct 29, 2008 at Beth Israel Medical Center and St. Luke's-Roosevelt Hospital Center. The study was closed by the IRB on 10/12/2018 due to low enrollment. The last date of study data collection was 11/19/2015.
Pre-assignment details
Subjects were not enrolled to the control group; data was retrospectively collected by viewing the charts of 20 patients who received Plasma Exchange
Participants by arm
| Arm | Count |
|---|---|
| Danazol, Plex, Steroids Everyone will receive Danazol with plasma exchange and corticosteroids
Danazol: Danazol 600 mg PO will be initiated with plasma exchange and corticosteroids at the time of enrollment. | 9 |
| Historic Control The subjects were not enrolled to the control group; data was retrospectively collected by viewing the charts of 20 patients who received Plasma Exchange | 0 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Danazol, Plex, Steroids | Total |
|---|---|---|
| Age, Continuous | 51.2 years STANDARD_DEVIATION 13.8 | 51.2 years STANDARD_DEVIATION 13.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 9 | 0 / 0 |
| other Total, other adverse events | 0 / 9 | 0 / 0 |
| serious Total, serious adverse events | 2 / 9 | 0 / 0 |
Outcome results
Primary
Number of Plasma Exchanges
The total number of plasma exchanges performed after initiation of the first plasma exchange.
Time frame: up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Danazol, Plex, Steroids | Number of Plasma Exchanges | 14.8 exchanges | Standard Deviation 9.64 |
| Historic Control | Number of Plasma Exchanges | 16.1 exchanges | Standard Deviation 8.93 |
Secondary
Length of Stay
Time frame: up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Danazol, Plex, Steroids | Length of Stay | 27.3 days | Standard Deviation 17.7 |
| Historic Control | Length of Stay | 24.9 days | Standard Deviation 13.1 |
Secondary
Number of Participants With Complete and Continuous Response Rate
Time frame: At 2 Years
Population: Two of the 20 historical controls did not have data for hospitalization days or time to remission, therefore computed complete response rates among the 18 patients for whom full data was available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Danazol, Plex, Steroids | Number of Participants With Complete and Continuous Response Rate | Complete Response Rate | 9 Participants |
| Danazol, Plex, Steroids | Number of Participants With Complete and Continuous Response Rate | Continuous Response Rate | 8 Participants |
| Historic Control | Number of Participants With Complete and Continuous Response Rate | Complete Response Rate | 17 Participants |
| Historic Control | Number of Participants With Complete and Continuous Response Rate | Continuous Response Rate | 16 Participants |
Secondary
Number of Participants With Relapses
Number of participants with relapses
Time frame: up to 12 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Danazol, Plex, Steroids | Number of Participants With Relapses | 1 Participants |
| Historic Control | Number of Participants With Relapses | 4 Participants |
Secondary
Number of Relapses
Number of relapses
Time frame: up to 12 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Danazol, Plex, Steroids | Number of Relapses | 1 relapses |
| Historic Control | Number of Relapses | 6 relapses |
Secondary
Time to Relapse
Time frame: up to 12 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Danazol, Plex, Steroids | Time to Relapse | 43 months |
| Historic Control | Time to Relapse | 28.5 months |
Secondary
Time to Remission
Time frame: up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Danazol, Plex, Steroids | Time to Remission | 11.4 days | Standard Deviation 5.05 |
| Historic Control | Time to Remission | 11.0 days | Standard Deviation 7.06 |