Trial · NCT00423319
Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)
NCT00423319, Phase 3, Completed, Bristol-Myers Squibb; results first posted 2014-05-14
3 sourcestrials-2026-11-12-0.4.0
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ConductScience Library. Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3). Trials, record NCT00423319. Release trials-2026-11-12-0.4.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00423319
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)
- NCT number
- NCT00423319
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 5,407 participants, actual
- Lead sponsor
- Bristol-Myers Squibb
- Conditions
- Deep Vein Thrombosis, Pulmonary Embolism
- Interventions
- Enoxaparin, Apixaban, Enoxaparin-matching placebo, Apixaban-matching placebo
- First posted
- 2007-01-18
- Last updated
- 2014-05-14
- Results first posted
- 2014-05-14
Source ClinicalTrials.gov
Registered outcomes14
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period | Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose | Event rate=Number of events divided by the number of patients evaluated. A mandatory bilateral ascending contrast venogram was to be obtained on Day 35 (± 3). Patients with confirmed symptomatic DVT at any time, or asymptomatic DVT upon venography, were to receive treatment for DVT according to the investigator's standard of care. Signs and symptoms suggestive of VTE included, but were not limited to: 1) lower extremity DVT: erythema, warmth, pain, swelling, tenderness; and 2) PE: pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended Treatment Period started on day of randomization and, for patients who received treatment, ended at the later of 2 days after last dose of study drug or 38 days after the first dose (presurgery) of study drug. For randomized patients who did not receive study drug, the period ended 38 days after randomization. |
| Secondary | Rate of Composite of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During Intended Treatment Period | Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose | Event rate=Number of events divided by the number of patients evaluated. Each patient was categorized as having no proximal DVT, having proximal DVT, being nonevaluable for proximal DVT, having no distal DVT, having distal DVT, or being nonevaluable for distal DVT. Adjudication criteria were: Normal=All deep veins were visualized, and there was no intraluminal filling defect (ILFD). ILFD=An area of reduced, or absent filling, at least partially surrounded with contrast medium in ≥ 2 projections or a lack of filling in a vessel in which there was a cut-off that had the configuration of a thrombus. Indeterminate=A lack of filling of a region of the deep vein system, proximal or distal, without the presence of an ILFD elsewhere in the same region. Not Done=A venography was not performed. Proximal DVT was found if any of the proximal veins had an ILFD. Pulmonary embolism was radiographically (angiography, V/Q scan, computed tomography) determined. |
| Secondary | Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period | Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose | VTE=venous thromboembolic event; VTE-related death=combination of fatal or nonfatal PE and symptomatic or asymptomatic DVT. Event rate=Number of events divided by the number of patients evaluated. |
| Secondary | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period | First dose of study drug (presurgery) through 2 days after the last dose of study drug | Event rate=Number of events divided by the number of patients evaluated. Major bleeding event defined as a bleeding event that was 1) Acute clinically overt bleeding accompanied by at least 1 of the following: decrease in hemoglobin of ≥ 2 g/dL over a 24-hour period, transfusion of ≥2 units of packed red blood cells; bleeding that occurred in at least 1 of the following sites: intracranial, intra-spinal, intraocular, pericardial, an operated joint and requires reoperation or intervention, intramuscular with compartment syndrome, or retroperitoneal; 2) Fatal. CRNM was defined as acute clinically overt bleeding that did not satisfy the criteria for a major bleeding event and met at least 1 of the following: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, or hemoptysis. Minor bleeding was defined as an acute clinically overt bleeding event that did not meet the criteria for major bleeding or a CRNM. Fatal bleeding event was defined as bleeding that was the primary |
| Secondary | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome | First dose of study drug (presurgery) through 30 days after the last dose of study drug | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. All suspected bleeding events were to be reported by the investigator as either an AE or SAE and adjudicated by the Independent Central Adjudication Committee (ICAC). Definitions of bleeding outcomes: Acute clinically overt bleeding =new onset, visible bleeding, or signs or symptoms suggestive of bleeding with confirmatory imaging techniques that could detect the presence of blood. |
| Secondary | Number of Participants With a Bleeding-related Adverse Event During the Treatment Period | First dose of study drug (presurgery) through 2 days after the last dose of study drug | All suspected bleeding events were to be reported by the investigator as either an adverse event or serious adverse event or and adjudicated by the Independent Central Adjudication Committee (ICAC). Definitions of bleeding outcomes: Acute clinically overt bleeding =new onset, visible bleeding, or signs or symptoms suggestive of bleeding with confirmatory imaging techniques that could detect the presence of blood. All acute clinically overt bleeding events were adjudicated by the ICAC as a major bleeding event or a clinically relevant nonmajor bleeding event; suspected minor bleeding events were not sent for adjudication. |
| Secondary | Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued) | First dose of study drug (presurgery) through 2 days after the last dose of study drug | All suspected bleeding events were to be reported by the investigator as either an adverse event or serious adverse event or and adjudicated by the Independent Central Adjudication Committee (ICAC). Definitions of bleeding outcomes: Acute clinically overt bleeding =new onset, visible bleeding, or signs or symptoms suggestive of bleeding with confirmatory imaging techniques that could detect the presence of blood. All acute clinically overt bleeding events were adjudicated by the ICAC as a major bleeding event or a clinically relevant nonmajor bleeding event; suspected minor bleeding events were not sent for adjudication. |
| Secondary | Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued) | First dose of study drug (presurgery) through 2 days after the last dose of study drug | All suspected bleeding events were to be reported by the investigator as either an adverse event or serious adverse event or and adjudicated by the Independent Central Adjudication Committee (ICAC). Definitions of bleeding outcomes: Acute clinically overt bleeding =new onset, visible bleeding, or signs or symptoms suggestive of bleeding with confirmatory imaging techniques that could detect the presence of blood. All acute clinically overt bleeding events were adjudicated by the ICAC as a major bleeding event or a clinically relevant nonmajor bleeding event; suspected minor bleeding events were not sent for adjudication. |
| Secondary | Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period | First dose of study drug (presurgery) through 2 days after the last dose of study drug | Neurologic events were based on Medical Dictionary for Regulatory Activities search categories.For new or worsening events that were not related to the site of surgery, additional information was collected on a specific form. In addition, neurology consultation was to be obtained for these patients. |
| Secondary | Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period | First dose of study drug (presurgery) through 2 days after the last dose of study drug | preRx=predose; LLN=lower limit of normal; ULN=upper limit of normal. MA criteria: Hemoglobin: \>2 g/dL decrease from preRx or value ≤ 8 g/dL; hematocrit (%): \<0.75\*preRx; platelet count (\*10\^9 cells/L): \<100,000/mm\^3; erythrocytes (\*10\^6 cells/μL): \<0.75\*preRx level; leukocytes (\*10\^3 cells/μL): \< 0.75\*LLN or \>1.25\*ULN, or if preRx LLN use \< 0.8\*preRx or \>ULN if preRx \>ULN use \>1.2\*preRx or \<LLN; basophils (\*10\^3 cells/μL): \>400/mm\^3; eosinophils (\*10\^3 cells/μL): \> 0.75\*10\^3 cells/μL; lymphocytes (\*10\^3 cells/μL): \>0.75\*10\^3 cells/μL; monocytes (\*10\^3 cells/μL): \>2000/mm\^3; neutrophils (\*10\^3 cells/μL): \<1.0; |
1 to 10 of 14Source ClinicalTrials.gov
See all 14 registered outcomesOutcomes14
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period | Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose | All randomized participants who, during the Intended Treatment Period, had an adjudicated and evaluable bilateral venogram, had an adjudicated venous thromboembolic event, or died of any cause. | Percentage of events/patients evaluated | NUMBER |
| SECONDARY | Rate of Composite of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During Intended Treatment Period | Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose | Randomized participants with either an adjudicated event or an adjudicated evaluable bilateral venogram | Percentage of events/patients evaluated | NUMBER |
| SECONDARY | Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period | Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose | All participants randomized to treatment | Percentage of events/patients evaluated | NUMBER |
| SECONDARY | Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period | First dose of study drug (presurgery) through 2 days after the last dose of study drug | All participants who received at least 1 dose of study drug | Percentage of events/patients evaluted | NUMBER |
| SECONDARY | Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome | First dose of study drug (presurgery) through 30 days after the last dose of study drug | All participants who received at least 1 dose of study medication | Participants | NUMBER |
| SECONDARY | Number of Participants With a Bleeding-related Adverse Event During the Treatment Period | First dose of study drug (presurgery) through 2 days after the last dose of study drug | All participants who received at least 1 dose of study drug | Participants | NUMBER |
| SECONDARY | Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued) | First dose of study drug (presurgery) through 2 days after the last dose of study drug | All participants who received at least 1 dose of study drug | Participants | NUMBER |
| SECONDARY | Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued) | First dose of study drug (presurgery) through 2 days after the last dose of study drug | All participants who received at least 1 dose of study drug | Participants | NUMBER |
| SECONDARY | Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period | First dose of study drug (presurgery) through 2 days after the last dose of study drug | All participants who received at least 1 dose of study drug | Participants | NUMBER |
| SECONDARY | Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period | First dose of study drug (presurgery) through 2 days after the last dose of study drug | All participants who received at least 1 dose of study drug | Participants | NUMBER |
1 to 10 of 14Source ClinicalTrials.gov
See all 14 outcomesResults by group322
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period | Apixaban, 2.5 mg BID Plus Placebo | 1.39 | 95% Confidence Interval 0.95 to 2.02 | Percentage of events/patients evaluated | |
Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period | Enoxaparin, 40 mg QD Plus Placebo | 3.86 | 95% Confidence Interval 3.08 to 4.83 | Percentage of events/patients evaluated | |
| Rate of Composite of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During Intended Treatment Period | Apixaban, 2.5 mg BID Plus Placebo | 0.45 | 95% Confidence Interval 0.24 to 0.85 | Percentage of events/patients evaluated | |
| Rate of Composite of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During Intended Treatment Period | Enoxaparin, 40 mg QD Plus Placebo | 1.14 | 95% Confidence Interval 0.77 to 1.69 | Percentage of events/patients evaluated | |
Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period | Apixaban, 2.5 mg BID Plus Placebo | All-cause death | 0.11 | Percentage of events/patients evaluated | |
Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period | Enoxaparin, 40 mg QD Plus Placebo | All-cause death | 0.04 | Percentage of events/patients evaluated | |
Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period | Apixaban, 2.5 mg BID Plus Placebo | VTE-related death | 0.04 | Percentage of events/patients evaluated | |
Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period | Enoxaparin, 40 mg QD Plus Placebo | VTE-related death | 0.00 | Percentage of events/patients evaluated | |
Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period | Apixaban, 2.5 mg BID Plus Placebo | PE (fatal or nonfatal) | 0.11 | Percentage of events/patients evaluated | |
Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period | Enoxaparin, 40 mg QD Plus Placebo | PE (fatal or nonfatal) | 0.19 | Percentage of events/patients evaluated |
1 to 10 of 322Source ClinicalTrials.gov
See all 322 results by groupParticipant flow8
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Apixaban, 2.5 mg BID Plus Placebo | 2,708 | |
| Overall Study | STARTED | Enoxaparin, 40 mg QD Plus Placebo | 2,699 | |
| Overall Study | Participants Who Received Treatment | Apixaban, 2.5 mg BID Plus Placebo | 2,673 | |
| Overall Study | Participants Who Received Treatment | Enoxaparin, 40 mg QD Plus Placebo | 2,659 | |
| Overall Study | COMPLETED | Apixaban, 2.5 mg BID Plus Placebo | 2,484 | |
| Overall Study | COMPLETED | Enoxaparin, 40 mg QD Plus Placebo | 2,447 | |
| Overall Study | NOT COMPLETED | Apixaban, 2.5 mg BID Plus Placebo | 224 | |
| Overall Study | NOT COMPLETED | Enoxaparin, 40 mg QD Plus Placebo | 252 |
Source ClinicalTrials.gov
Adverse events372
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Procedural pain | Injury, poisoning and procedural complications | Apixaban, 2.5 mg BID + Placebo | 421 | 2,673 | |
| other | Procedural pain | Injury, poisoning and procedural complications | Enoxaparin, 40 mg QD + Placebo | 426 | 2,659 | |
| other | Dizziness | Nervous system disorders | Apixaban, 2.5 mg BID + Placebo | 185 | 2,673 | |
| other | Dizziness | Nervous system disorders | Enoxaparin, 40 mg QD + Placebo | 154 | 2,659 | |
| other | Insomnia | Psychiatric disorders | Apixaban, 2.5 mg BID + Placebo | 138 | 2,673 | |
| other | Insomnia | Psychiatric disorders | Enoxaparin, 40 mg QD + Placebo | 132 | 2,659 | |
| other | Tachycardia | Cardiac disorders | Apixaban, 2.5 mg BID + Placebo | 123 | 2,673 | |
| other | Tachycardia | Cardiac disorders | Enoxaparin, 40 mg QD + Placebo | 137 | 2,659 | |
| other | Oedema peripheral | General disorders | Apixaban, 2.5 mg BID + Placebo | 156 | 2,673 | |
| other | Oedema peripheral | General disorders | Enoxaparin, 40 mg QD + Placebo | 141 | 2,659 |
1 to 10 of 372Source ClinicalTrials.gov
See all 372 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Apixaban, 2.5 mg BID + Placebo | ||
| Total, all-cause mortality | Enoxaparin, 40 mg QD + Placebo | ||
| Total, other adverse events | Apixaban, 2.5 mg BID + Placebo | 1,260 | 2,673 |
| Total, other adverse events | Enoxaparin, 40 mg QD + Placebo | 1,315 | 2,659 |
| Total, serious adverse events | Apixaban, 2.5 mg BID + Placebo | 184 | 2,673 |
| Total, serious adverse events | Enoxaparin, 40 mg QD + Placebo | 172 | 2,659 |
Source ClinicalTrials.gov
Papers3
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons1
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison |
|---|
| Apixaban, 2.5 mg BID + Placebo vs Enoxaparin, 40 mg QD + Placebo: serious adverse events |
Source Trial comparisons
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Source
- Release
- trials-2026-11-12-0.4.0
- Release manifest SHA-256
- 0f4a8d8c48aee2a7573ae0fa94ecbeab70c1adbe449bbc95c424bc7d3e97b9d4
- Registry capture
- 2026-11-12
- Results copy, AACT
- 2026-03-23
- NIH clinical studies file
- 2026-11-13
Source ClinicalTrials.gov
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNone stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
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GET https://conductscience.org/api/trials/v1/NCT00423319/results?page=2