Optimal Platelet Dose Strategy for Management of Thrombocytopenia

NCT00128713 | Completed Phase 3 Results DMC

• 18 other identifiers: 238U01HL072268U01HL072028U01HL072033U01HL072072U01HL072191U01HL072196U01HL072248U01HL072274U01HL072283U01HL072289U01HL072290U01HL072291U01HL072305U01HL072331U01HL072346U01HL072355U01HL072359
• Study Type: interventional
• Target: 1,351
• Locations: 1 country
• Sites: 21

Brief Summary

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).

Conditions

Thrombocytopenia

Keywords

Blood Transfusion; Blood Platelets

Outcome Measures

Primary Outcomes (1)

• At Least One Day With Grade 2 or Higher Bleeding

  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

  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)

Secondary Outcomes (4)

• Platelet Utilization

  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)

• Number of Platelet Transfusion Episodes

  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)

• Bleeding Severity, if a Suitable Scale is Validated and Published by the Time the Trial Ends

  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)

• Highest Grade of Bleeding While on Study

  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)

Study Arms (3)

1

ACTIVE COMPARATOR

Lower Dose Prophylactic Platelets

Procedure: Lower Dose Prophylactic Platelet Transfusions

2

ACTIVE COMPARATOR

Medium Dose Prophylactic Platelets

Procedure: Medium Dose Prophylactic Platelet Transfusions

3

ACTIVE COMPARATOR

Higher Dose Prophylactic Platelets

Procedure: Higher Dose Prophylactic Platelet Transfusions

Interventions

Medium Dose Prophylactic Platelet Transfusions PROCEDURE

2.2 x 10\^11 platelets per m\^2 BSA

2

Lower Dose Prophylactic Platelet Transfusions PROCEDURE

1.1 x 10\^11 platelets per m\^2 BSA

1

Higher Dose Prophylactic Platelet Transfusions PROCEDURE

4.4 \* 10\^11 platelets per m\^2 BSA

3

Eligibility Criteria

• Age: Up to 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• PT less than or equal to 1.3 times the upper limit of normal for the laboratory
• PTT less than or equal to 1.3 times the upper limit of normal for the laboratory
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Carelon Research: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Transfusion Medicine/Hemostasis Clinical Research Network: collaborator

Study Sites (21)

Emory University Hospitals; Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Tulane University Hospital and Clinics

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Children's Hospital Boston; Beth Israel Deaconess Medical Center; Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, 55455, United States

Location

NY-Presbyterian Hosp/Weill Cornell Medical Center

New York, New York, 10021, United States

Location

University of North Carolina Hospitals

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Hospital Cleveland

Cleveland, Ohio, 44106, United States

Location

U of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

U of Pennsylvania Health System; Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Presbyterian and Shadyside Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

U of Texas SW Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Virginia Mason Hospital

Seattle, Washington, 98101, United States

Location

U of Washington Medical Center/FHCRC; Children's Hospital and Medical Center

Seattle, Washington, 98104, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53201, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53201, United States

Location

Oncology Alliance/St. Luke's Hospital

Milwaukee, Wisconsin, 53215, United States

Location

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (4)

• Uhl L, Assmann SF, Hamza TH, Harrison RW, Gernsheimer T, Slichter SJ. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood. 2017 Sep 7;130(10):1247-1258. doi: 10.1182/blood-2017-01-757930. Epub 2017 Jul 5.

  PMID: 28679741 DERIVED

• Josephson CD, Granger S, Assmann SF, Castillejo MI, Strauss RG, Slichter SJ, Steiner ME, Journeycake JM, Thornburg CD, Bussel J, Grabowski EF, Neufeld EJ, Savage W, Sloan SR. Bleeding risks are higher in children versus adults given prophylactic platelet transfusions for treatment-induced hypoproliferative thrombocytopenia. Blood. 2012 Jul 26;120(4):748-60. doi: 10.1182/blood-2011-11-389569. Epub 2012 Apr 26.

  PMID: 22538854 DERIVED

• Triulzi DJ, Assmann SF, Strauss RG, Ness PM, Hess JR, Kaufman RM, Granger S, Slichter SJ. The impact of platelet transfusion characteristics on posttransfusion platelet increments and clinical bleeding in patients with hypoproliferative thrombocytopenia. Blood. 2012 Jun 7;119(23):5553-62. doi: 10.1182/blood-2011-11-393165. Epub 2012 Apr 10.

  PMID: 22496156 DERIVED

• Slichter SJ, Kaufman RM, Assmann SF, McCullough J, Triulzi DJ, Strauss RG, Gernsheimer TB, Ness PM, Brecher ME, Josephson CD, Konkle BA, Woodson RD, Ortel TL, Hillyer CD, Skerrett DL, McCrae KR, Sloan SR, Uhl L, George JN, Aquino VM, Manno CS, McFarland JG, Hess JR, Leissinger C, Granger S. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med. 2010 Feb 18;362(7):600-13. doi: 10.1056/NEJMoa0904084.

  PMID: 20164484 DERIVED

MeSH Terms

Conditions

Thrombocytopenia

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Results Point of Contact

• Title: Susan Assmann, PhD
• Organization: New England Research Institutes

sassmann@neriscience.com

617-923-7747

Study Officials

• 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, Baltimore

  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

  PRINCIPAL INVESTIGATOR

• Jeffrey McCullough, MD

  University of Minnesota

  STUDY CHAIR

• Janice G. McFarland, MD

  Versiti Blood Health

  PRINCIPAL INVESTIGATOR

• Paul M. Ness, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Ellis Neufeld, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Thomas L. Ortel, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

• Sherrill J. Slichter, MD

  Bloodworks

  STUDY CHAIR

• Ronald G. Strauss, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

• Darrell J. Triulzi, MD

  University of Pittsburgh Presbyterian and Shadyside Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2005
• First Posted: August 10, 2005
• Study Start: July 1, 2004
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: October 28, 2015
• Results First Posted: July 16, 2009

Record last verified: 2013-08

Locations

US (21)