Fragmin for the Treatment of Acute VTE in Pediatric Cancer Patients
- Registration Number
- NCT00952380
- Lead Sponsor
- Pfizer
- Brief Summary
Three month treatment of acute VTE with Fragmin in pediatric cancer patients
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single Arm dalteparin Single arm open-label
- Primary Outcome Measures
Name Time Method Median Dose of Dalteparin Required to Achieve Prespecified Therapeutic Anti- Factor Xa Level 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
Name Time Method Time to First Occurrence of Symptomatic Recurrent Venous Thromboembolism (VTE) 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.
Number of Participants With New or Progressive Symptomatic Venous Thromboembolism (VTE) 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.
Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DSBP) in Participants Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 Absolute Values of Height of Participants Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 Number of Dose Adjustments Required to Achieve Prespecified Therapeutic Anti-Xa Levels 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.
Percentage of Participants Who Achieved Prespecified Therapeutic Anti- Factor Xa Levels 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.
Absolute Values of Weight of Participants Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 Percentage of Participants With Anti-Factor Xa Levels Outside the Prespecified Range at Day 30, 60 and 90 in Follow up Phase 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.
Maintenance Dose of Dalteparin Required to Achieve Prespecified Therapeutic Anti- Factor Xa Levels 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.
Percentage of Participants With Clinical Response of Progression, Regression, Resolution and No Change in Venous Thromboembolism (VTE) 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.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) 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.
Number of Participants With Laboratory Abnormalities 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.
Absolute Values of Body Length of Participants Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 Percentage of Participants With Major and Minor Bleeding Event 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).
Absolute Values of Heart Rate (HR) and Pulse Rate (PR) of Participants 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.
Absolute Values of Body Temperature of Participants Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 Absolute Values of Respiratory Rate of Participants Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 Respiratory rate was defined as the number of breaths per minute.
Number of Participants With Physical Examination Abnormalities of Participants 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.
Time to First Occurrence of Major Bleeding Event 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).
Time to Achieve Prespecified Therapeutic Anti- Factor Xa Levels 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.
Percentage of Participants Who Remained Within Prespecified Therapeutic Anti-Factor Xa Levels at Day 30, 60 and 90 in Follow up Phase 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.
Trial Locations
- Locations (26)
Lekarna, Univerzitetni klinicni center Ljubljana
🇸🇮Ljubljana, Slovenia
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Investigational Drug Service Tampa General Hospital
🇺🇸Tampa, Florida, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
SAHI "Children's Republican Clinical Hospital of the Ministry of
🇷🇺Kazan, Republic Tatarstan, Russian Federation
Hospital HM Universitario Monteprincipe
🇪🇸Boadilla del Monte, Madrid, Spain
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Tampa General Hospital Center of Research Excellence
🇺🇸Tampa, Florida, United States
Wolfson Children's Hospital
🇺🇸Jacksonville, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
St. Joseph's Children's Hospital of Tampa
🇺🇸Tampa, Florida, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
El Paso Children's Hospital
🇺🇸El Paso, Texas, United States
Texas Children's Cancer and Hematology Centers
🇺🇸Houston, Texas, United States
Oslo universitetssykehus HF
🇳🇴Oslo, Norway
Texas Tech University Health Sciences Center El Paso
🇺🇸El Paso, Texas, United States
Texas Children's Hospital Investigational Pharmacy Services
🇺🇸Houston, Texas, United States
Sykehusapoteket Oslo
🇳🇴Oslo, Norway
FSBEI HE Kazan SMU of Minzdrav Russia
🇷🇺Kazan, Republic Tatarstan, Russian Federation
SBHI of Moscow city Morozovskaya Children City Clinical Hospital of Moscow city
🇷🇺Moscow, Russian Federation
Pediatricna klinika, Univerzitetni Klinicni Center Ljubljana
🇸🇮Ljubljana, Slovenia
Hospital HM Universitario Monteprincipe Servicio de Farmacia
🇪🇸Boadilla del Monte, Madrid, Spain