A Study of Dalteparin Prophylaxis in High-Risk Ambulatory Cancer Patients

NCT00876915 | Terminated Phase 3 Results DMC

• 2 other identifiers: 253871R01HL095109-01
• Study Type: interventional
• Target: 218
• Locations: 2 countries
• Sites: 7

Brief 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. 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.

Conditions

Venous Thromboembolism; Pulmonary Embolism

Keywords

prevention of VTE and PE in high risk cancer patients

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  13 weeks

Secondary Outcomes (6)

• The Value of Tissue Factor (TF) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients

  baseline value of tissue factor

• The Value of D-Dimer at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients

  baseline value of D-Dimer

• The Value of Human F12 at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients

  baseline value of Human F12

• The Value of Tissue Factor Pathway Inhibitor (TFPI) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients

  baseline value of TFPI

• The Value of Factor VIIa (FVIIa) at Baseline Prior to Chemotherapy in Ambulatory Cancer Patients

  baseline value of FVIIa

Study Arms (3)

High Risk for VTE recieving dalteparin

EXPERIMENTAL

Patients assigned at random to receive prophylactic dalteparin injections

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

Interventions

dalteparin injection DRUG

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).

Also known as: Fragmin

High Risk for VTE recieving dalteparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Rochester: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Eisai Inc.: collaborator

Study Sites (7)

University of California, Davis

Sacramento, California, 95817, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Rochester General Hospital

Rochester, New York, 14621, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27705, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ottawa Hospital Research Institute (OHRI)

Ottawa, Ontario, K1H 8L6, Canada

Location

Related Publications (2)

• 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.

  PMID: 33337539 DERIVED

• 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.

  PMID: 28139259 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism; Pulmonary Embolism

Interventions

Dalteparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Charles Francis, MD
• Organization: University of Rochester

charles_francis@urmc.rochester.edu

(585) 275-5823

Study Officials

• Charles W. Francis, MD

  Univeristy of Rochester Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor emeritus

Study Record Dates

• First Submitted: March 31, 2009
• First Posted: April 7, 2009
• Study Start: July 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: December 1, 2014
• Last Updated: November 24, 2015
• Results First Posted: October 12, 2015

Record last verified: 2015-10

Locations

US (6); CA (1)