Optimal Platelet Dose Strategy for Management of Thrombocytopenia
| Status: | Completed |
|---|---|
| Conditions: | Hematology, Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | Any - 100 |
| Updated: | 4/21/2016 |
| Start Date: | July 2004 |
| End Date: | January 2008 |
Determination of the Optimal Prophylactic Platelet Dose Strategy to Prevent Bleeding in Thrombocytopenic Patients (A TMH CTN Study)
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).
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).
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.
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.
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
We found this trial at
21
sites
Click here to add this to my saved trials
Click here to add this to my saved trials
University of Maryland Medical Center Founded in 1823 as the Baltimore Infirmary, the University of...
Click here to add this to my saved trials
Johns Hopkins Hospital Patients are the focus of everything we do at The Johns Hopkins...
Click here to add this to my saved trials
Boston, Massachusetts 02115
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
Click here to add this to my saved trials
University of Iowa Hospitals and Clinics University of Iowa Hospitals and Clinics—recognized as one of...
Click here to add this to my saved trials
600 Highland Ave
Madison, Wisconsin 53792
Madison, Wisconsin 53792
(608) 263-6400
University of Wisconsin Hospital and Clinics UW Health strives to meet the health needs of...
Click here to add this to my saved trials
9000 W Wisconsin Ave #270
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
(414) 266-2000
Children's Hospital of Wisconsin Nothing matters more than our children. At Children's Hospital of Wisconsin,...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
2450 Riverside Ave
Minneapolis, Minnesota 55454
Minneapolis, Minnesota 55454
(612) 273-3000
University of Minnesota Medical Center, Fairview Improving patients' lives drives the innovation that makes University...
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Philadelphia, Pennsylvania 19104
Click here to add this to my saved trials
Click here to add this to my saved trials
1959 Northeast Pacific Street
Seattle, Washington 98104
Seattle, Washington 98104
Click here to add this to my saved trials