Venous ThromboembolismPhase 3PHACSNCT00876915
A Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients
A Phase 3 study testing dalteparin injection in people with Venous Thromboembolism and Pulmonary Embolism, run by University of Rochester at 7 sites in 2 countries.
Trial summary
Some cancer patients starting a new chemotherapy regimen are likely to develop blood clots, also known as venous thromboembolism (VTE). Blood clots can cause symptoms and can occasionally be life-threatening. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism, Pulmonary Embolism
- What is being tested?
- dalteparin injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 218 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Jul 2009to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Cleveland Clinic
Cleveland, Ohio, 44195
Duke University School of Medicine
Durham, North Carolina, 27705
Rochester General Hospital
Rochester, New York, 14621
University of Rochester Medical Center
Rochester, New York, 14642
University of California, Davis
Sacramento, California, 95817
Canada1 site
Ottawa Hospital Research Institute (OHRI)
Ottawa, Ontario, K1H 8L6
About this study
Official title: A Prospective Randomized Multicenter Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients
Some cancer patients starting a new chemotherapy regimen are likely to develop blood clots, also known as venous thromboembolism (VTE). Blood clots can cause symptoms and can occasionally be life-threatening. The purpose of this study is to determine if a daily injection of a blood-thinner, dalteparin, for 12 weeks can safely and effectively reduce the frequency of blood clots. Dalteparin is currently approved for prevention of blood clots following surgery and in hospitalized patients but not specifically for cancer outpatients.
Read the 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.
- Conditions
- Venous Thromboembolism, Pulmonary Embolism
- Being tested
- dalteparin injection
- Keywords
- prevention of VTE and PE in high risk cancer patients
- Medical subject headings
- Venous Thromboembolism, Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dalteparin injectionDrug
Also called Fragmin
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).
| Study group | Role | What they receive |
|---|---|---|
| High Risk for VTE recieving dalteparin | Experimental | Patients assigned at random to receive prophylactic dalteparin injections Receives: Drug: dalteparin injection |
| High Risk for VTE No therapy | No intervention | No prophylactic therapy for VTE prevention given (Subjects receiving standard of care) |
| Low Risk for VTE | No intervention | Used as a control for the secondary outcome of evaluating tissue factor in collected blood samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With Venous Thromboembolisms
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.
Measured: 12 weeks
Percentage of Patients Who Experienced Clinically Significant Bleeding Events.
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.
Measured: 13 weeks
Secondary outcomes (6)
The Value of Tissue Factor (TF) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
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.
Measured: baseline value of tissue factor
The Value of D-Dimer at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
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
Measured: baseline value of D-Dimer
The Value of Human F12 at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
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
Measured: baseline value of Human F12
The Value of Tissue Factor Pathway Inhibitor (TFPI) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
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
Measured: baseline value of TFPI
The Value of Factor VIIa (FVIIa) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
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
Measured: baseline value of FVIIa
The Value of Thrombin Antithrombin (TAT) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
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
Measured: baseline value of TAT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2009 (estimated)
- Study startJul 2009
- Primary completionJul 2014
- Study completionDec 2014
Why it stopped: slow enrollment and lack of continuing funds
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 218 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Eisai Inc.
- Responsible party
- Principal investigator, Charles Francis, University of Rochester
- Investigators
- Charles W. Francis, MD, Principal investigator, Univeristy of Rochester Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00876915
- Sponsor's protocol ID
- 25387
- Other IDs
- 1R01HL095109-01
- Acronym
- PHACS
- Status last verified
- Oct 2015
- First submitted
- 31 Mar 2009
- Last updated
- 24 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 33337539Khorana 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.
PubMed 28139259
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Multicenter Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients
- ClinicalTrials.gov ID
- NCT00876915
- Acronym / sponsor ID
- PHACS / 25387
- Conditions
- Venous Thromboembolism, Pulmonary Embolism
- Keywords
- prevention of VTE and PE in high risk cancer patients
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow enrollment and lack of continuing funds
- Enrolment
- 218 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Eisai Inc.
- Study start
- Jul 2009
- Primary completion
- Jul 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 7 Apr 2009 (estimated)
- Results
- Posted 12 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Some cancer patients starting a new chemotherapy regimen are likely to develop blood clots, also known as venous thromboembolism (VTE). Blood clots can cause symptoms and can occasionally be life-threatening. The purpose of this study is to determine if a daily injection of a blood-thinner, dalteparin, for 12 weeks can safely and effectively reduce the frequency of blood clots. Dalteparin is currently approved for prevention of blood clots following surgery and in hospitalized patients but not specifically for cancer outpatients.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High Risk for VTE recieving dalteparin | Experimental | Drug: dalteparin injectionPatients assigned at random to receive prophylactic dalteparin injections |
| High Risk for VTE No therapy | No intervention | –No prophylactic therapy for VTE prevention given (Subjects receiving standard of care) |
| Low Risk for VTE | No intervention | –Used as a control for the secondary outcome of evaluating tissue factor in collected blood samples |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dalteparin injectionAlso: FragminPotency 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). | Drug | High Risk for VTE recieving dalteparin |
Primary outcome
Percentage of Patients With Venous Thromboembolisms
Time frame: 12 weeks
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.
Percentage of Patients Who Experienced Clinically Significant Bleeding Events.
Time frame: 13 weeks
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.
6 secondary outcomes
The Value of Tissue Factor (TF) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time frame: baseline value of tissue factor
The Value of D-Dimer at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time frame: baseline value of D-Dimer
The Value of Human F12 at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time frame: baseline value of Human F12
The Value of Tissue Factor Pathway Inhibitor (TFPI) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time frame: baseline value of TFPI
The Value of Factor VIIa (FVIIa) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time frame: baseline value of FVIIa
The Value of Thrombin Antithrombin (TAT) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients
Time frame: baseline value of TAT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33337539Rutjes 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.
- Derived from this study: PubMed 28139259Khorana 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles W. Francis, MD principal investigator
Univeristy of Rochester Medical Center
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing dalteparin injection in people with Venous Thromboembolism and Pulmonary Embolism, run by University of Rochester at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With Venous Thromboembolisms (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00876915, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2015.