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STAR - Study of TTP and Rituximab, A Randomized Clinical Trial

Phase 3
12 Years
Not Enrolling
Thrombotic Thrombocytopenic Purpura

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Trial Information

STAR - Study of TTP and Rituximab, A Randomized Clinical Trial

TTP is a disorder that causes blood clots to form in the small blood vessels throughout the
body. If the clots in fact block the blood vessels, blood flow is restricted to various
organs, including the brain, kidneys, and heart. This can lead to neurological problems,
stroke, abnormal kidney function, and heart problems. Because a large number of platelets
are used in the blood clotting process, people with TTP have a reduced number of platelets
circulating in their blood. They also have fewer red blood cells circulating in their blood
because the red blood cells break down prematurely as blood squeezes past a blood clot.

The primary treatment for TTP is plasmapheresis, also called plasma exchange, which is a
procedure that circulates a person's blood through a machine that first removes the damaged
plasma and then adds healthy donor plasma into the blood. Next, patients receive a blood
transfusion with the new blood. Corticosteroids, a type of medication that reduces the
amount of antibodies a person's body makes, are also commonly used in conjunction with
plasma exchange to treat TTP. Plasma exchange is usually effective, with platelet and red
blood cell counts returning to normal after the procedure is complete. However, some people
do experience a relapse of TTP and will require repeat plasma exchanges. Rituximab, an
antibody currently used to treat lymphoma and rheumatoid arthritis, may improve immune
system response and decrease the number of days needed to undergo the plasma exchange
procedure. The purpose of this study is to evaluate the effectiveness of rituximab in
combination with plasma exchange at improving an early treatment response in people with TTP
and decreasing the likelihood of a relapse of TTP.

This 3-year study will enroll people who have recently been diagnosed with TTP or recently
experienced a relapse and have not yet had six plasma exchanges during the current episode
of TTP. Participants will be randomly assigned to receive either plasma exchanges and
corticosteroids or plasma exchanges, corticosteroids, and rituximab. Blood will be collected
from participants at baseline and each day they undergo the plasma exchange procedure. All
participants will receive a plasma exchange every day until their platelet counts are normal
and signs of tissue damage have improved. Participants will receive corticosteroid
medication every day until plasma exchange is stopped, at which time the dosage will be
gradually tapered until 7 weeks after the last plasma exchange. Participants receiving
rituximab will receive the first dose intravenously within 7 days of the first plasma
exchange; they will continue to receive rituximab once a week for 4 weeks. After the plasma
exchanges are completed, all participants will have routine follow-up care with their
doctors to make sure there is no TTP relapse. In the 1 year after study entry, additional
blood collections will occur at varying times. Study researchers will monitor participants'
health in the 3 years after study entry by following up with their doctors or through
periodic phone calls. A portion of blood will be collected and stored for future TTP
research purposes; this is optional.

Inclusion Criteria:

- Differential or admission diagnosis of TTP-like syndrome, defined as the following:

1. Platelet count of less than 80,000/µL for newly diagnosed patients and less than
120,000/µL for relapsed patients

2. Microangiopathic hemolytic anemia (MHA) with red blood cell fragmentation

3. Lactate dehydrogenase (LDH) level greater than two times the upper limit of
normal for newly diagnosed patients and greater than the upper limit of normal
for relapsed patients

- Receiving or will receive treatment for TTP with plasma exchange

- Has not started the sixth plasma exchange in the current TTP episode

Exclusion Criteria:

- Treated for TTP in the 2 months before study entry

- Previously enrolled in this study

- Severe active infection indicated by sepsis (requirement for pressors with or without
positive blood cultures) or clinical evidence of enteric infection with E. coli 0157
or related organism

- Currently under treatment for cancer or has a current diagnosis of cancer (other than
localized skin carcinoma)

- Microangiopathic hemolytic anemia due to a mechanical heart valve

- Severe high blood pressure, as defined by systolic blood pressure of greater than 180
and diastolic blood pressure of greater than 120, or papilledema

- Has ever had an organ or stem cell transplant

- Has received calcineurin inhibitors (e.g., sirolimus, tacrolimus, cyclosporin A) in
the 6 months before TTP diagnosis

- Diagnosis of disseminated intravascular coagulation (DIC), defined as the following:

1. International normalized ratio (INR) level greater than 2.0 (unrelated to
anticoagulation, unresponsive to vitamin K administration) OR

2. Fibrinogen less than 100 mg/dL

- Pregnant

- Requires ventilator assistance or intravenous pressors for treatment of TTP. If no
longer required prior to study entry, patient is eligible for the study.

- Known congenital TTP or family history of TTP

- Established diagnosis of lupus, and/or actively treated for lupus in the 60 days
before study entry. In addition, people with two or more of the following systemic
lupus erythematosus (SLE) clinical criteria in the 60 days before study entry will be

1. Characteristic skin rash, either malar or photosensitive

2. Symmetric polyarthritis

3. Serositis, either pleurisy or pericarditis

- Previously received rituximab

- Has taken the following drugs known to be associated with TTP-like syndrome in the 3
months before study entry: clopidogrel (Plavix), ticlopidine (Ticlid), or quinine

- Will receive more than 1.5 plasma volumes per day after study entry

- HIV history or positive serology

- History of hepatitis B or positive serology for HBsAg or Anti-HBc

- History of hepatitis C

- Known persistent or unexplained platelet count below 150,000/µL in the 3 months
before current TTP episode

- Known hypersensitivities or allergies to murine and/or humanized antibodies

- Currently participating in trials of investigational therapies or devices (other than
investigational central catheters)

- Has ever had a diagnosis of ventricular tachycardia

- Acute transmural heart attack during the current hospital admission

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Role of rituximab in increasing early treatment response in participants with TTP who are also treated with plasma exchange and corticosteroids

Outcome Time Frame:

Measured at Day 52

Safety Issue:


Principal Investigator

Susan F. Assmann, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

New England Research Institutes, Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

April 2009

Completion Date:

February 2010

Related Keywords:

  • Thrombotic Thrombocytopenic Purpura
  • TTP
  • Rituximab
  • Plasma Exchange
  • Purpura
  • Purpura, Thrombocytopenic
  • Purpura, Thrombotic Thrombocytopenic



University of IowaIowa City, Iowa  52242
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Brigham and Women's HospitalBoston, Massachusetts  02115
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Froedtert Memorial Lutheran HospitalMilwaukee, Wisconsin  53226
Children's Hospital BostonBoston, Massachusetts  02115
University of PennsylvaniaPhiladelphia, Pennsylvania  19104
Duke University Medical CenterDurham, North Carolina  27710
Emory UniversityAtlanta, Georgia  30322
University of Alabama, BirminghamBirmingham, Alabama  35233
Tulane University Health Sciences CenterNew Orleans, Louisiana  70112
University of North Carolina HospitalsChapel Hill, North Carolina  27599
University of Maryland Medical CenterBaltimore, Maryland  21201-1595
Integris Baptist Medical CenterOklahoma City, Oklahoma  73112
Johns Hopkins HospitalBaltimore, Maryland  21287
Gunderson Clinic, LtdLa Crosse, Wisconsin  54601
Puget Sound Blood CenterSeattle, Washington  98014
University of Wisconsin at MadisonMadison, Wisconsin  53792
New York-Presbyterian Hospital/Weill Cornell Medical CenterNew York, New York  10021
University Hospital ClevelandCleveland, Ohio  44106
University of Pittsburgh Presbyterian and Shadyside HospitalPittsburgh, Pennsylvania  15213