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Trial record 1 of 1 for:    NCT00952380
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Fragmin for the Treatment of Acute VTE in Pediatric Cancer Patients

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ClinicalTrials.gov Identifier: NCT00952380
Recruitment Status : Completed
First Posted : August 6, 2009
Results First Posted : April 15, 2019
Last Update Posted : April 15, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
Three month treatment of acute VTE with Fragmin in pediatric cancer patients

Condition or disease Intervention/treatment Phase
Venous Thromboembolism Drug: dalteparin Phase 2

Detailed Description:
Primary study objectives include are to determine the pharmacodynamic (PD) profiles for treatment doses of dalteparin in pediatric subjects of different ages with cancer and venous thromboembolism (VTE), using anti-Xa (Xa) levels and a population PD analysis methodology, and to determine the median dose required to achieve therapeutic anti- Xa levels (0.5 to 1.0 International Units [IU]/mL) based on subject age and weight.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A THREE MONTH PROSPECTIVE OPEN LABEL STUDY OF THERAPY WITH FRAGMIN(REGISTERED) (DALTEPARIN SODIUM INJECTION) IN CHILDREN WITH VENOUS THROMBOEMBOLISM WITH OR WITHOUT MALIGNANCIES
Actual Study Start Date : August 2009
Actual Primary Completion Date : March 2018
Actual Study Completion Date : March 2018

Arm Intervention/treatment
Single Arm
Single arm open-label
Drug: dalteparin
dalteparin subcutaneous injection




Primary Outcome Measures :
  1. Median Dose of Dalteparin Required to Achieve Prespecified Therapeutic Anti- Factor Xa Level [ Time Frame: 4 hours post-dose at each Day 1 to 7 in dose adjustment phase ]
    Prespecified therapeutic anti-factor Xa level was 0.5-1.0 international unit per milliliter (IU/mL). Cumulative data of Day 1 to 7 has been reported.


Secondary Outcome Measures :
  1. Percentage of Participants Who Achieved Prespecified Therapeutic Anti- Factor Xa Levels [ Time Frame: Day 1 to 7 in dose adjustment phase ]
    Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. Percentage of participants who achieved the prespecified level during the dose adjustment phase were reported in this outcome measure.

  2. Number of Participants With New or Progressive Symptomatic Venous Thromboembolism (VTE) [ Time Frame: Baseline up to 28 days after the last dose of study drug (up to Day 132) ]
    Symptomatic VTE defined as new or progressive signs and symptoms as judged by the investigator including but not limited to: objective swelling, pain or tenderness, pitting edema, erythema or cyanosis. Progression of VTE: Progression of clot burden in terms of severity of occlusion, or involvement of new venous segments at any time after the initial diagnosis.

  3. Time to First Occurrence of Symptomatic Recurrent Venous Thromboembolism (VTE) [ Time Frame: Baseline up to 28 days after the last dose of study drug (up to Day 132) ]
    It was defined as the time interval (in days) between date of first study treatment and date of documentation of first VTE. VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot breaks, loose and travels in the blood, this is called VTE. VTE was confirmed by at least one radiographic test and was defined as any new or progressive VTE whose signs and symptoms (identified by the investigator) included: objective swelling or tenderness, pitting edema, erythema or cyanosis.

  4. Percentage of Participants With Clinical Response of Progression, Regression, Resolution and No Change in Venous Thromboembolism (VTE) [ Time Frame: Baseline up to 28 days after the last dose of study drug (up to Day 132) ]
    VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. PE is a blood clot in the lungs. Clinical response of progression was defined as progression of clot burden in terms of severity of occlusion, or involvement of new venous segments at any time after the initial diagnosis. Clinical response of regression: Regressed clot burden utilizing the same imaging modality as the screening visit. Clinical response of resolution: Thrombus resolution of the qualifying event measured by repeat imaging at the end of study (EOS) visit.

  5. Percentage of Participants With Major and Minor Bleeding Event [ Time Frame: Baseline up to 28 days after the last dose of study drug (up to Day 132) ]
    A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: fatal bleeding, bleeding accompanied by a decrease in hemoglobin of at least 2 grams per deciliter 24 hours, Overt bleeding deemed by the attending physician to necessitate permanent discontinuation of trial medication, Overt bleeding deemed by the attending physician to be unrelated to the participant's underlying condition and accompanied by blood product administration or bleeding occurred at a critical site (intraocular, intracranial, retroperitoneal). A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major or clinically relevant no major bleeding (bleeding resulting in any medical or surgical interventions but which did not meet the criteria for major bleeding).

  6. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after the last dose of study drug (up to Day 132) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after the last dose of study drug (up to Day 132) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.

  7. Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to 104 days ]
    Criteria:hematology:hemoglobin, hematocrit, erythrocytes less than(<)0.8*lower limit of normal(LLN), platelets <0.5*LLN >1.75*upper limit of normal (ULN),leukocytes <0.6* LLN >1.5* ULN, lymphocytes, lymphocytes/Leukocytes, neutrophils, neutrophils/leukocytes <0.8* LLN >1.2* ULN, basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes monocytes monocytes/leukocytes >1.2*ULN, activated partial thromboplastin time, prothrombin time, prothrombin international normalized ratio >1.1* ULN. Clinical chemistry: bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase >3.0*ULN, protein, albumin <0.8* LLN >1.2* ULN, blood urea nitrogen, creatinine >1.3* ULN, sodium <0.95*LLN >1.05*ULN, potassium, chloride, calcium, magnesium <0.9* LLN >1.1* ULN, phosphate <0.8* LLN >1.2* ULN, glucose <0.6*LLN >1.5*ULN, estimated(est) creatinine clearance, est GFR modified and bedside schwartz, >1.0* ULN. Urinalysis: creatinine >1.0*ULN.

  8. Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DSBP) in Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
  9. Absolute Values of Heart Rate (HR) and Pulse Rate (PR) of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
    Heart rate and pulse rate of participants were measured in terms of beats per minute.

  10. Absolute Values of Height of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
  11. Absolute Values of Weight of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
  12. Absolute Values of Respiratory Rate of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
    Respiratory rate was defined as the number of breaths per minute.

  13. Absolute Values of Body Temperature of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
  14. Absolute Values of Body Length of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
  15. Number of Participants With Physical Examination Abnormalities of Participants [ Time Frame: Screening, Visit 2 (Baseline), Visit 3 (Day 1), Visit 4 (Day 2), Visit 5 (Day 30), Visit 6 (Day 60), Visit 7 (Day 90) ]
    Physical examinations included head, eyes, ears, nose, throat, neck, heart, chest, lungs, abdomen, extremities, skin, neurological status and general appearance. Abnormality in physical examination was based on investigator's discretion. Only those categories in which at least 1 participant had abnormality were reported.

  16. Time to First Occurrence of Major Bleeding Event [ Time Frame: Baseline up to 28 days after the last dose of study drug (up to Day 132) ]
    Time to first occurrence of major bleeding event was defined as the time interval (in days) between date of first study treatment and date of documentation of first major bleeding event. A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: fatal bleeding, bleeding accompanied by a decrease in hemoglobin of at least 2 grams per deciliter, overt bleeding deemed by the attending physician to necessitate permanent discontinuation of trial medication, overt bleeding deemed by the attending physician to be unrelated to the participant's underlying condition and accompanied by blood product administration, bleeding occurred at a critical site (intraocular, intracranial, retroperitoneal or intraspinal).

  17. Percentage of Participants Who Remained Within Prespecified Therapeutic Anti-Factor Xa Levels at Day 30, 60 and 90 in Follow up Phase [ Time Frame: Day 30, Day 60, Day 90 in follow up phase ]
    Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. The percentage of participants who had anti factor-Xa levels within the prespecified therapeutic range at Day 30, 60 and 90 during the follow up phase were reported in this outcome measure.

  18. Percentage of Participants With Anti-Factor Xa Levels Outside the Prespecified Range at Day 30, 60 and 90 in Follow up Phase [ Time Frame: Day 30, Day 60, Day 90 in follow-up phase ]
    Prespecified therapeutic anti-factor Xa range was 0.5-1.0 IU/mL. The percentage of participants who had anti-factor Xa levels outside the prespecified therapeutic range at Day 30, 60 and 90 during the follow up phase were reported in this outcome measure.

  19. Maintenance Dose of Dalteparin Required to Achieve Prespecified Therapeutic Anti- Factor Xa Levels [ Time Frame: 4 hours post-dose at each Day 1 to 7 in dose adjustment phase ]
    Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. Cumulative data for day 1 to 7 has been reported.

  20. Time to Achieve Prespecified Therapeutic Anti- Factor Xa Levels [ Time Frame: Day 1 to 7 in dose adjustment phase ]
    Time to achieve the target range (prespecified therapeutic anti- factor Xa levels) was defined as the number of days from the first dose of study drug to the final dose that achieves the target anti-factor Xa level. Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. Cumulative data of Day 1 to 7 is reported.

  21. Number of Dose Adjustments Required to Achieve Prespecified Therapeutic Anti-Xa Levels [ Time Frame: 4 hours post-dose at each Day 1 to 7 in dose adjustment phase ]
    During dose adjustment phase, doses were adjusted according to prespecified therapeutic anti-Xa levels in order to achieve target prespecified therapeutic anti-factor Xa levels (0.5 to 1.0 IU/mL). Number of dose adjustments which were done within the specified time window of up to 4 hours post dose on all days (1 to 7) to achieve the prespecified therapeutic anti-Xa levels are reported.


Other Outcome Measures:
  1. Total Body Clearance of Dalteparin [ Time Frame: 4 hours post-dose at each Day 1 to 7 in dose adjustment phase ]
    Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed.

  2. Volume of Distribution of Dalteparin [ Time Frame: 4 hours post-dose at each Day 1 to 7 in dose adjustment phase ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

  3. Absorption Rate Constant (Ka) of Dalteparin [ Time Frame: 4 hours post-dose at each Day 1 to 7 in dose adjustment phase ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

-

Exclusion Criteria:

-


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00952380


Locations
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United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
MedStar Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Florida
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Wolfson Children's Hospital
Jacksonville, Florida, United States, 32207
Investigational Drug Service Tampa General Hospital
Tampa, Florida, United States, 33606
Tampa General Hospital Center of Research Excellence
Tampa, Florida, United States, 33606
Tampa General Hospital
Tampa, Florida, United States, 33606
University of South Florida
Tampa, Florida, United States, 33606
St. Joseph's Children's Hospital of Tampa
Tampa, Florida, United States, 33607
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
El Paso Children's Hospital
El Paso, Texas, United States, 79905
Texas Tech University Health Sciences Center El Paso
El Paso, Texas, United States, 79905
Texas Children's Cancer and Hematology Centers
Houston, Texas, United States, 77030
Texas Children's Hospital Investigational Pharmacy Services
Houston, Texas, United States, 77030
Texas Children's Hospital
Houston, Texas, United States, 77030
Norway
Sykehusapoteket Oslo
Oslo, Norway, 0372
Oslo universitetssykehus HF
Oslo, Norway, 0424
Russian Federation
FSBEI HE Kazan SMU of Minzdrav Russia
Kazan, Republic Tatarstan, Russian Federation, 420012
SAHI "Children's Republican Clinical Hospital of the Ministry of
Kazan, Republic Tatarstan, Russian Federation, 420138
SBHI of Moscow city Morozovskaya Children City Clinical Hospital of Moscow city
Moscow, Russian Federation, 119049
Slovenia
Lekarna, Univerzitetni klinicni center Ljubljana
Ljubljana, Slovenia, SI-1000
Pediatricna klinika, Univerzitetni Klinicni Center Ljubljana
Ljubljana, Slovenia, SI-1000
Spain
Hospital HM Universitario Monteprincipe Servicio de Farmacia
Boadilla del Monte, Madrid, Spain, 28660
Hospital HM Universitario Monteprincipe
Boadilla del Monte, Madrid, Spain, 28660
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] October 18, 2016
Statistical Analysis Plan  [PDF] November 18, 2015


Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00952380     History of Changes
Other Study ID Numbers: FRAG-A001-201
A6301094 ( Other Identifier: Alias Study Number )
2016‐000394‐21 ( EudraCT Number )
2016-000394-21 ( EudraCT Number )
First Posted: August 6, 2009    Key Record Dates
Results First Posted: April 15, 2019
Last Update Posted: April 15, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Keywords provided by Pfizer:
VTE
Additional relevant MeSH terms:
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Thromboembolism
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Dalteparin
Heparin, Low-Molecular-Weight
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action