The primary study objective is to compare the three study arms of medium, lower and higher dose platelet therapy with respect to the percentage of patients experiencing at least one episode of Grade 2 or higher bleeding as determined by the Platelet Dose Trial Bleeding Scale. (Generally speaking, Grade 2 bleeding corresponds to bleeding that is moderate, but not severe enough to warrant red blood cell transfusion.)

There are a number of secondary endpoints related to platelet transfusions, hemostasis, and other concerns. The four most important secondary endpoints compare the three study arms with respect to the following outcomes:

Platelet utilization rates (total number of platelets transfused x 10 ^11).

Number of platelet transfusion events; i.e., frequency of transfusions. A transfusion event would be each separate platelet transfusion issued by the trial site''''s transfusion service.

Highest category of bleeding during time on study (Platelet Dose Trial Bleeding Scale Grades <= 1, 2, 3, 4 by arm).

Bleeding severity based on number of days with bleeding (total days of bleeding and bleeding/thrombocytopenic day), intensity of bleeding, and number of sites with bleeding, if such a severity score has been validated and published by the time this trial is completed.

Condition	Intervention	Phase
Blood transfusion Blood Platelets	Procedure: Platelet Transfusion	Phase III

Further Study Details: 

BACKGROUND:

It is important to identify the most safe and cost effective strategies for providing platelet support to achieve effective disease management without depleting platelet supplies. Informative clinical data have been provided concerning the platelet transfusion trigger. In contrast, the optimal quantity of platelets to be used per transfusion remains a highly controversial subject. No prospective platelet transfusion trials have been performed in which patients are randomized to an assigned platelet dose throughout their period of thrombocytopenia.

DESIGN NARRATIVE:

After obtaining consent and verifying eligibility requirements, the study staff randomize the patient to one of three doses for prophylactic platelet transfusions (lower, medium, and higher dose). Dosage is based on the patient''''s body surface area (BSA). The dose targets are as follows: the lower dose is 1.1 x 10^11/m^2, the medium dose is 2.2 x 10^11/m^2, and the higher dose is 4.4 x 10^11/m^2. A dose within 25% of this value in either direction is considered to be in the target range. For many adult patients, the typical dose of one unit of apheresis platelets would fall in the target range for the medium dose. All prophylactic transfusions provided while the patient is on study should be given according to the randomized target dose range. Only blood bank staff, not clinical staff, have access to the target dose range for each patient.

Every day the patient is on study, a morning platelet count will be taken. If this value is less than or equal to 10,000, a prophylactic platelet transfusion should be given. Otherwise, no prophylactic platelet transfusion should be given that day. Platelet transfusions may be given at any time, and at any dose, to treat active bleeding or in association with an invasive procedure. Every day, a hemostatic assessment will be carried out to identify any bleeding the patient may experience. This assessment involves a patient interview, physical assessment, and chart reviewed by a trained clinical professional. Data on all transfusions (platelet, red blood cell, and other), all transfusion-related events, all serious adverse events, and protocol deviations are also recorded.

Patients will be followed until 30 days after the initial platelet transfusion, until they have not received a platelet transfusion for 10 days after the most recent platelet transfusion, or until hospital discharge, whichever comes first.

Because each of the three pairwise dose comparisons is of interest, the primary and secondary endpoints will each be analyzed using three separate pairwise comparisons, each at the 0.017 significance level to adjust for multiple comparisons.

The study has been approved by the NHLBI-appointed Protocol Review Committee and Data and Safety Monitoring Board and each participating institution''''s Institutional Review Board. An interim monitoring plan was developed by the Protocol Team and DSMB, and is described in the protocol. The study is being monitored in accordance with this plan.

Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Patients with, or expected to have, hypoproliferative thrombocytopenia who are expected to have a platelet count of <= 10,000 ul for >= 5 days, and be in the hospital for >= 5 days.

Weight between 10 and 135 kilograms.

Patients whose PT/INR, PTT and fibrinogen assays, measured within 72 hours before study entry, are as follows:

1. PT <=1.3 X upper limit of normal for the laboratory
2. PTT <= 1.3 X upper limit of normal for the laboratory
3. Fibrinogen >= 100 mg/dL

Patients with any diagnosis undergoing or with completed hematopoietic stem cell transplantation, and patients with a diagnosis of acute or chronic leukemia, non-Hodgkins and Hodgkins lymphoma, myeloma, myelodysplasia, or non-hematologic malignancy undergoing or with completed chemotherapy.

During this hospitalization, the patient has not yet received any platelet transfusions related to the current or planned course of therapy. Individual platelet transfusions given prior to the study and unrelated to thrombocytopenia will not exclude the patient.

Exclusion Criteria

Evidence of >= Grade 2 bleeding (as determined by the Platelet Dose Trial Bleeding Scale) while being assessed for study entry.

Patients receiving antithrombotic drugs.

Patients who will receive bedside leukoreduced platelet transfusions.

Presently with or with a history of platelet transfusion refractoriness within 30 days prior to enrollment in the study.

Pre-enrollment lymphocytotoxic antibody screen (PRA) known to be >= 20% based on prior data. If antibody screen not available, enroll patient.

Presently with or a history of acute promyelocytic leukemia (APML), immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), or hemolytic-uremic syndrome (HUS).

Patients who will be transfused at platelet trigger of > 10,000 platelets/ul.

Patients with recent history of major surgery (<= 2 weeks).

Currently taking, or participating in a clinical trial involving, platelet substitutes, platelet growth factors, or pharmacologic agents intended to enhance or decrease platelet hemostatic function.

Patients who are pregnant.

Patients previously enrolled in this trial.

Please refer to this study by ClinicalTrials.gov identifier  NCT00128713

Georgia
      Emory University Hospitals;Children''''s Healthcare of Atlanta, Atlanta,  Georgia,  30322,  United States; Recruiting
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States; Recruiting
Louisiana
      Tulane University Hospital and Clinics, New Orleans,  Louisiana,  70112,  United States; Recruiting
Maryland
      Johns Hopkins Hospital, Baltimore,  Maryland,  21287,  United States; Recruiting
      University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Massachusetts
      Children''''s Hospital Boston; Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02115,  United States; Recruiting
Minnesota
      University of Minnesota Medical Center, Fairview, Minneapolis,  Minnesota,  55455,  United States; Recruiting
New York
      NY-Presbyterian Hosp/Weill Cornell Medical Center, New York,  New York,  10021,  United States; Recruiting
North Carolina
      Duke University Medical Center, Durham,  North Carolina,  27710,  United States; Recruiting
      University of North Carolina Hospitals, Chapel Hill,  North Carolina,  USA,  United States; Recruiting
Ohio
      University Hospitals of Cleveland, Cleveland,  Ohio,  44106,  United States; Recruiting
Oklahoma
      U of Oklahoma Health Sciences Center; U of Texas SW Medical Center at Dallas, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Pennsylvania
      University of Pittsburgh Presbyterian and Shadyside Hospital, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
      U of Pennsylvania Health System; Children''''s Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
Washington
      U of Washington Medical Center/FHCRC; Children''''s Hospital and Medical Center, Seattle,  Washington,  98104,  United States; Recruiting
Wisconsin
      University of Wisconsin Hospital and Clinics, Milwaukee,  Wisconsin,  53201,  United States; Recruiting

Study chairs or principal investigators

Susan Assmann,  New England Research Institutes, Inc.   
Mark Brecher,  University of North Carolina   
James Bussel,  NY-Presbyterian Hosp/Weill Cornell Medical Center   
James George,  U of Oklahoma Health Sciences Center; U of Texas SW Medical Center at Dallas   
John Hess,  University of Maryland Medical Center   
Christopher Hillyer,  Emory University Hospitals;Children''''s Healthcare of Atlanta   
Barbara Konkle,  U of Pennsylvania Health System; Children''''s Hospital of Philadelphia   
Cindy Leissinger,  Tulane University Hospital and Clinics   
Keith McCrae,  University Hospitals of Cleveland   
Jeffrey McCullough,  University of Minnesota Medical Center, Fairview   
Janice McFarland,  University of Wisconsin Hospital and Clinics   
Paul Ness,  Johns Hopkins University   
Ellis Neufeld,  Children''''s Hospital Boston; Beth Israel Deaconess Medical Center   
Thomas Ortel,  Duke University   
Sherrill Slichter,  U of Washington Medical Center/FHCRC; Children''''s Hospital and Medical Center   
Ronald Strauss,  University of Iowa   
Darrell Triulzi,  University of Pittsburgh Presbyterian and Shadyside Hospital   

Study ID Numbers:  238
Last Updated:  August 9, 2005
Record first received:  August 8, 2005
ClinicalTrials.gov Identifier:  NCT00128713
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-23