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Optimal Platelet Dose Strategy for Management of Thrombocytopenia (PLADO)

This study has been completed.
Sponsor:
Collaborators:
Transfusion Medicine/Hemostasis Clinical Research Network
Information provided by:
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT00128713
First received: August 8, 2005
Last updated: August 2, 2013
Last verified: August 2013
  Purpose

The primary objective of this study is to compare the three study arms of lower, medium, 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 (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 will compare the three study arms with respect to the following outcomes: 1) platelet utilization rates (total number of platelets transfused x 10 ^11); 2) number of platelet transfusion events (frequency of transfusions); a transfusion event would be defined as each separate platelet transfusion issued by the study site's transfusion service; 3) highest category of bleeding during time of study (Platelet Dose Trial Bleeding Scale Grades less than or equal to 1, 2, 3, or 4 by arm); and 4) 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 the study is completed).


Condition Intervention Phase
Thrombocytopenia
Procedure: Medium Dose Prophylactic Platelet Transfusions
Procedure: Lower Dose Prophylactic Platelet Transfusions
Procedure: Higher Dose Prophylactic Platelet Transfusions
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Determination of the Optimal Prophylactic Platelet Dose Strategy to Prevent Bleeding in Thrombocytopenic Patients (A TMH CTN Study)

Resource links provided by NLM:


Further study details as provided by New England Research Institutes:

Primary Outcome Measures:
  • At Least One Day With Grade 2 or Higher Bleeding [ Time Frame: From randomization until the subject ends the study (10 days after most recent platelet transfusion, 30 days after first platelet transfusion on study, or hospital discharge, whichever occurs first) ] [ Designated as safety issue: Yes ]
    Any Grade 2 (moderate) or higher grade bleeding, as determined by daily hemostatic assessment and documentation of any red blood cell transfusions to treat bleeding


Secondary Outcome Measures:
  • Platelet Utilization [ Time Frame: From randomization until the subject ends the study (10 days after most recent platelet transfusion, 30 days after first platelet transfusion on study, or hospital discharge, whichever occurs first) ] [ Designated as safety issue: No ]
    Total number of platelets transfused, based on attempted dose, among subjects who have at least one platelet transfusion and no missing data on attempted doses.

  • Number of Platelet Transfusion Episodes [ Time Frame: From randomization until the subject ends the study (10 days after most recent platelet transfusion, 30 days after first platelet transfusion on study, or hospital discharge, whichever occurs first) ] [ Designated as safety issue: No ]
    Number of platelet transfusion episodes among subjects who have at least one platelet transfusion and no missing data on attempted doses.

  • Bleeding Severity, if a Suitable Scale is Validated and Published by the Time the Trial Ends [ Time Frame: From randomization until the subject ends the study (10 days after most recent platelet transfusion, 30 days after first platelet transfusion on study, or hospital discharge, whichever occurs first) ] [ Designated as safety issue: Yes ]
    No suitable scale was identified, so no analyses for this outcome were carried out

  • Highest Grade of Bleeding While on Study [ Time Frame: From randomization until the subject ends the study (10 days after most recent platelet transfusion, 30 days after first platelet transfusion on study, or hospital discharge, whichever occurs first) ] [ Designated as safety issue: Yes ]
    Highest grade of bleeding during time on study using Platelet Dose Trial modification of World Health Organization Bleeding Scale. Grades 0-1 (no or minimal bleeding), 2 (moderate bleeding), 3 (bleeding generally requiring red cell transfusion), 4 (severe bleeding)


Enrollment: 1351
Study Start Date: July 2004
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Lower Dose Prophylactic Platelets
Procedure: Lower Dose Prophylactic Platelet Transfusions
1.1 x 10^11 platelets per m^2 BSA
Active Comparator: 2
Medium Dose Prophylactic Platelets
Procedure: Medium Dose Prophylactic Platelet Transfusions
2.2 x 10^11 platelets per m^2 BSA
Active Comparator: 3
Higher Dose Prophylactic Platelets
Procedure: Higher Dose Prophylactic Platelet Transfusions
4.4 * 10^11 platelets per m^2 BSA

Detailed Description:

BACKGROUND:

It is important to identify the safest and most cost effective strategies for providing platelet support that will 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 studies 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 patients will be randomized to one of three doses for prophylactic platelet transfusions (lower, medium, or higher dose). The dosage is based on the patient's body surface area (BSA). The dose targets are as follows: 1) the lower dose is 1.1 x 10^11/m²; 2) the medium dose is 2.2 x 10^11/m²; and 3) the higher dose is 4.4 x 10^11/m². 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 in the study will be given according to the randomized target dose range. Only blood bank staff, not clinical staff, will have access to the target dose range for each patient.

The patient's morning platelet count will be taken every day. If this value is less than or equal to 10,000, a prophylactic platelet transfusion will be given. Otherwise, no prophylactic platelet transfusion will 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. A hemostatic assessment will be carried out every day to identify any bleeding the patient may experience. This assessment involves a patient interview, physical assessment, and a chart review. Data on all transfusions (e.g., platelets and red blood cells), all transfusion-related events, all serious adverse events, and protocol deviations will also be recorded.

Patients will participate in the study either 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).

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

This study has been approved by the National Heart, Lung, and Blood Institute (NHLBI)-appointed protocol review committee and data and safety monitoring board (DSMB), 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has, or is expected to have, hypoproliferative thrombocytopenia, and is expected to have a platelet count of up to 10,000 ul for at least 5 days and be in the hospital for at least 5 days
  • Weight is between 10 and 135 kilograms
  • PT/INR, PTT, and fibrinogen assays that are measured within 72 hours before study entry are as follows:

    1. PT less than or equal to 1.3 times the upper limit of normal for the laboratory
    2. PTT less than or equal to 1.3 times the upper limit of normal for the laboratory
    3. Fibrinogen greater than or equal to 100 mg/dl
  • Undergoing, or has completed, hematopoietic stem cell transplantation, for any diagnosis; OR has a diagnosis of acute or chronic leukemia, non-Hodgkins or Hodgkins lymphoma, myeloma, myelodysplasia, or non-hematologic malignancy and is undergoing, or has 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 greater than or equal to Grade 2 bleeding (as determined by the Platelet Dose Trial Bleeding Scale)
  • Receiving antithrombotic drugs
  • Will receive bedside leuko-reduced platelet transfusions
  • Present, or history of, platelet transfusion refractoriness within 30 days prior to study entry
  • Pre-enrollment lymphocytotoxic antibody screen (PRA) known to be greater than or equal to 20% based on prior data
  • Present, or history of, acute promyelocytic leukemia (APML), immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), or hemolytic-uremic syndrome (HUS)
  • Will be transfused at platelet trigger of greater than 10,000 platelets/ul
  • Recent history of major surgery (within 2 weeks of study entry)
  • Currently taking, or participating in a study involving, platelet substitutes, platelet growth factors, or pharmacologic agents intended to enhance or decrease platelet hemostatic function
  • Pregnant
  • Previously enrolled in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00128713

Locations
United States, Georgia
Emory University Hospitals; Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Louisiana
Tulane University Hospital and Clinics
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Children's Hospital Boston; Beth Israel Deaconess Medical Center; Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota Medical Center, Fairview
Minneapolis, Minnesota, United States, 55455
United States, New York
NY-Presbyterian Hosp/Weill Cornell Medical Center
New York, New York, United States, 10021
United States, North Carolina
University of North Carolina Hospitals
Chapel Hill, North Carolina, United States, 27514
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University Hospital Cleveland
Cleveland, Ohio, United States, 44106
United States, Oklahoma
U of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
U of Pennsylvania Health System; Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Presbyterian and Shadyside Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
U of Texas SW Medical Center at Dallas
Dallas, Texas, United States, 75390
United States, Washington
U of Washington Medical Center/FHCRC; Children's Hospital and Medical Center
Seattle, Washington, United States, 98104
Virginia Mason Hospital
Seattle, Washington, United States, 98101
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53201
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53201
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, United States, 53226
Oncology Alliance/St. Luke's Hospital
Milwaukee, Wisconsin, United States, 53215
Sponsors and Collaborators
New England Research Institutes
Transfusion Medicine/Hemostasis Clinical Research Network
Investigators
Principal Investigator: Susan F. Assmann New England Research Institutes, Inc.
Principal Investigator: Mark Brecher, MD University of North Carolina
Principal Investigator: James B. Bussel, MD NY-Presbyterian Hosp/Weill Cornell Medical Center
Principal Investigator: James George, MD U of Oklahoma Health Sciences Center
Principal Investigator: John R. Hess University of Maryland
Principal Investigator: Christopher D. Hillyer, MD Emory University
Principal Investigator: Barbara A. Konkle, MD University of Pennsylvania
Principal Investigator: Cindy A. Leissinger, MD Tulane University
Principal Investigator: Keith R. McCrae, MD University Hospitals Cleveland
Study Chair: Jeffrey McCullough, MD University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Janice G. McFarland, MD Blood Center of Wisconsin
Principal Investigator: Paul M. Ness, MD Johns Hopkins University
Principal Investigator: Ellis Neufeld, MD, PhD Children's Hospital Boston
Principal Investigator: Thomas L. Ortel, MD, PhD Duke University
Study Chair: Sherrill J. Slichter, MD Puget Sound Blood Center
Principal Investigator: Ronald G. Strauss, MD University of Iowa
Principal Investigator: Darrell J. Triulzi, MD University of Pittsburgh Presbyterian and Shadyside Hospital
  More Information

No publications provided by New England Research Institutes

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Susan F. Assmann, New England Research Institutes
ClinicalTrials.gov Identifier: NCT00128713     History of Changes
Other Study ID Numbers: 238, U01HL072268, U01 HL072268, U01 HL72028, U01 HL72033, U01 HL72072, U01 HL72191, U01 HL72196, U01 HL72248, U01 HL72274, U01 HL72283, U01 HL72289, U01 HL72290, U01 HL72291, U01 HL72305, U01 HL72331, U01 HL72346, U01 HL72355, U01 HL72359
Study First Received: August 8, 2005
Results First Received: January 30, 2009
Last Updated: August 2, 2013
Health Authority: United States: Federal Government

Keywords provided by New England Research Institutes:
Blood Transfusion
Blood Platelets

Additional relevant MeSH terms:
Thrombocytopenia
Blood Platelet Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on November 23, 2014