- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00876915
A Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients (PHACS)
A Prospective Randomized Multicenter Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
VTE is an increasingly frequent complication of cancer and anti-cancer therapies. It is associated with increased mortality and other significant adverse consequences. Risk factors for VTE in the cancer population have been identified, and multiple studies have also shown that VTE can be prevented in high-risk populations with the use of thromboprophylaxis. This study evaluated the safety and efficacy of prophylaxis in a high-risk subgroup of cancer patients identified by a validated risk model developed by us previously called the "Khorana Score." Correlative studies evaluated the value of tissue factor as a predictive biomarker of VTE. The purpose of this study was to conduct a prospective, randomized clinical trial comparing the safety and efficacy of prophylaxis with dalteparin to no treatment in reducing VTE in high-risk ambulatory cancer patients initiating chemotherapy and to establish the value of TF as a predictive marker for VTE in ambulatory cancer patients receiving chemotherapy.
PHACS was a randomized multi-center clinical trial. Eligible patients were enrolled and underwent baseline screening ultrasonography of the lower extremities to rule out pre-existing DVT and a chest CT scan to rule out PE. If negative, patients were then randomized to receive either dalteparin 5000 units subcutaneously daily or observation for a study period of 12 weeks. The first day of dalteparin prophylaxis coincided with the first day of initiation of a new systemic chemotherapy regimen. The patients were seen every 4 weeks (±1 week) at the time of regularly scheduled chemotherapy cycle visits for serial ultrasonography of lower extremities during study period (i.e. at 4, 8 and 12 weeks.) A chest CT scan was performed at 12 weeks. Compliance was measured by asking patients about missed doses at these 4-weekly visits as well as by asking patients to fill an injection diary.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Ontario
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Ottawa, Ontario, Canada, K1H 8L6
- Ottawa Hospital Research Institute (OHRI)
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California
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Sacramento, California, United States, 95817
- University of California, Davis
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New York
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Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
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Rochester, New York, United States, 14642
- University of Rochester Medical Center
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Rochester, New York, United States, 14621
- Rochester General Hospital
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North Carolina
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Durham, North Carolina, United States, 27705
- Duke University School of Medicine
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- A histologic diagnosis of malignancy;
- At planned initiation of a new systemic chemotherapy regimen (including patients starting on first chemotherapy or patients previously treated but starting on a new regimen);
- A risk score for VTE ≥3 [assign score of 2 for very high risk sites of cancer (stomach, pancreas), score of 1 for high risk site (lung, lymphoma, gynecologic, bladder, testicular) and score of 0 for all other sites], hemoglobin <10 g/dL or planned use of erythropoiesis stimulating agents, platelet count ≥350,000/mm3, total leukocyte count > 11,000/mm3 or body mass index ≥ 35 kg/m2]. Any counts meeting criteria drawn within 2 weeks prior to enrollment are considered acceptable.
- Age 18 years or older
- Provide written, informed consent.
Exclusion Criteria:
- Active bleeding or at high risk of serious bleeding complication in the opinion of the investigator
- Diagnosis of primary brain tumor multiple myeloma, leukemia, or myelodysplastic syndrome
- Planned stem cell transplant
- Life expectancy < 6 months
- Known allergy to heparin or LMWH
- Patient or caregiver incapable of daily self-injection
- Acute or chronic renal insufficiency with creatinine clearance < 30 mL/min
- History of heparin-induced thrombocytopenia
- Allergy to contrast agents
- Pregnancy
- Need for anticoagulant therapy
- Platelet count < 75,000/mm3
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: High Risk for VTE recieving dalteparin
Patients assigned at random to receive prophylactic dalteparin injections
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Potency is described in international anti-Xa units (IU).
One unit (anti-Xa) of dalteparin sodium, average molecular weight 5,000, corresponds to the activity of one unit of the 1st International Standard for Low Molecular Weight Heparin (LMWH)with respect to inhibition of coagulation Factor Xa in plasma utilizing the chromogenic peptide substrate S-2765 (N-alpha-Benzyloxycarbonyl-D-arginyl-glycyl-arginine-pNA.2HCl).
Other Names:
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No Intervention: High Risk for VTE No therapy
No prophylactic therapy for VTE prevention given (Subjects receiving standard of care)
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No Intervention: Low Risk for VTE
Used as a control for the secondary outcome of evaluating tissue factor in collected blood samples
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Patients With Venous Thromboembolisms
Time Frame: 12 weeks
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The percentage of patients who developed a Venous thromboembolism were recorded within 12 weeks following randomization including all adjudicated occurrences of symptomatic DVT, PE and upper extremity thrombus as well as all asymptomatic DVT and PE detected by lower extremity ultrasonography and chest CT.
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12 weeks
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Percentage of Patients Who Experienced Clinically Significant Bleeding Events.
Time Frame: 13 weeks
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The percentage of patients who experienced a clinically significant bleeding event were recorded (including major and clinically significant non-major bleeding) over 13 weeks (12 weeks of study and an additional week of observation).
Major bleeding was defined as being clinically overt and satisfying one of the following: decrease in hemoglobin of 2.0 g/dL, leading to transfusion of 2 or more units of blood or packed red cells, occurring in a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial) or leading to death.
Clinically significant non-major bleeding was defined as clinically overt, not meeting criteria for major bleeding and with one of the following characteristics: multiple-source, spontaneous hematoma > 25 cm², epistaxis > 5 mins, macroscopic hematuria not related to instrumentation, spontaneous rectal bleeding, gingival bleeding > 5 mins, hemoptysis, hematemesis or prolonged bleeding (> 5 minutes) after venipuncture.
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13 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Value of Tissue Factor (TF) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time Frame: baseline value of tissue factor
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Blood samples were obtained to measure the value of Tissue Factor at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients.
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baseline value of tissue factor
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The Value of D-Dimer at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time Frame: baseline value of D-Dimer
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Blood samples were obtained to measure the value of D-Dimer at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients
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baseline value of D-Dimer
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The Value of Human F12 at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time Frame: baseline value of Human F12
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Blood samples were obtained to measure the value of Human F12 at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients
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baseline value of Human F12
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The Value of Tissue Factor Pathway Inhibitor (TFPI) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time Frame: baseline value of TFPI
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Blood samples were obtained to measure the value of TFPI at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients
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baseline value of TFPI
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The Value of Factor VIIa (FVIIa) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time Frame: baseline value of FVIIa
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Blood samples were obtained to measure the value of FVIIa at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients
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baseline value of FVIIa
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The Value of Thrombin Antithrombin (TAT) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time Frame: baseline value of TAT
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Blood samples were obtained to measure the value of TAT at baseline compared between high risk for VTE and low risk for VTE ambulatory cancer patients
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baseline value of TAT
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Charles W. Francis, MD, Univeristy of Rochester Medical Center
Publications and helpful links
General Publications
- Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.
- Khorana AA, Francis CW, Kuderer NM, Carrier M, Ortel TL, Wun T, Rubens D, Hobbs S, Iyer R, Peterson D, Baran A, Kaproth-Joslin K, Lyman GH. Dalteparin thromboprophylaxis in cancer patients at high risk for venous thromboembolism: A randomized trial. Thromb Res. 2017 Mar;151:89-95. doi: 10.1016/j.thromres.2017.01.009. Epub 2017 Jan 26.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Embolism and Thrombosis
- Embolism
- Thromboembolism
- Venous Thromboembolism
- Pulmonary Embolism
- Molecular Mechanisms of Pharmacological Action
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Anticoagulants
- Heparin, Low-Molecular-Weight
- Tinzaparin
- Dalteparin
Other Study ID Numbers
- 25387
- 1R01HL095109-01 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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