Fragmin for the Treatment of Acute VTE in Pediatric Cancer Patients
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| ClinicalTrials.gov Identifier: NCT00952380 |
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Recruitment Status :
Completed
First Posted : August 6, 2009
Results First Posted : April 16, 2019
Last Update Posted : April 16, 2019
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Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
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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 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 38 participants |
| Allocation: | N/A |
| 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 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Single Arm
Single arm open-label
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Drug: dalteparin
dalteparin subcutaneous injection |
Primary Outcome Measures :
- 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 :
- 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.
- 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.
- 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.
- 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.
- 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).
- 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.
- 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.
- 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 ]
- 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.
- Absolute Values of Height of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
- Absolute Values of Weight of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
- 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.
- Absolute Values of Body Temperature of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
- Absolute Values of Body Length of Participants [ Time Frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90 ]
- 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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:
- 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.
- 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.
- 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
Show 26 study locations
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Study Documents (Full-Text)
Documents provided by Pfizer:
Documents provided by Pfizer:
Study Protocol [PDF] October 18, 2016
Statistical Analysis Plan [PDF] November 18, 2015
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT00952380 |
| Other Study ID Numbers: |
FRAG-A001-201 A6301094 ( Other Identifier: Alias Study Number ) 2016-000394-21 ( EudraCT Number ) |
| First Posted: | August 6, 2009 Key Record Dates |
| Results First Posted: | April 16, 2019 |
| Last Update Posted: | April 16, 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:
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VTE |
Additional relevant MeSH terms:
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Thromboembolism Venous Thromboembolism Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Dalteparin |
Tinzaparin Heparin, Low-Molecular-Weight Anticoagulants Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action |