Extended Prophylactic Anticoagulation Following Spinal Surgery for Metastatic Disease

Phase 4Not Yet RecruitingNCT07713875

James Bayley50 enrolled

Overview

People who have surgery on their spine to treat cancer that has spread (metastatic disease) have a high chance of developing dangerous blood clots in the legs or lungs. These blood clots are called deep vein thrombosis (DVT) or pulmonary embolism (PE). In a review of patients at UPMC who had this type of surgery, about 15 out of 100 developed a blood clot within 90 days of leaving the hospital. Right now, patients receive blood-thinning medicine only while they are in the hospital after surgery. Once they go home, the medicine is stopped. There are no guidelines telling doctors whether blood-thinning medicine should continue after patients go home from spine surgery for cancer. However, for other types of major cancer surgery, studies have shown that continuing blood-thinning medicine for about 4 weeks after surgery can help prevent blood clots. This study will test whether taking a blood-thinning medicine called apixaban (brand name Eliquis) by mouth for 30 days after leaving the hospital can help prevent blood clots in patients who have had spine surgery for cancer that has spread. The dose used in this study (2.5 mg twice a day) is the same dose approved by the U.S. Food and Drug Administration (FDA) for preventing blood clots after hip and knee replacement surgery. About 50 adults at UPMC will take part. Participants will take apixaban for 30 days starting the day after hospital discharge. The study team will call participants by phone three times - about 2 days, 31 days, and 91 days after discharge - to check on their health, ask about any bleeding or blood clot symptoms, and assess medication use. No extra clinic visits are required. Results will be compared to a group of 68 patients who had the same type of surgery in the past but did not take apixaban after leaving the hospital. The main goal is to find out if apixaban reduces the rate of blood clots within 90 days of hospital discharge. The study will also track bleeding events and other side effects to determine if this approach is safe. The study hypothesis is that extended blood-thinning medicine after surgery will reduce blood clots compared to the current approach of stopping this medicine at hospital discharge.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients undergoing surgery for metastatic spinal disease. Published series report 90-day symptomatic VTE rates of 11-15% in this population, with a substantial proportion of events occurring after hospital discharge when standard inpatient prophylaxis has ceased. Current guidelines from ASCO and ACCP recommend extended pharmacologic VTE prophylaxis (4 weeks postoperatively) following major abdominal and pelvic cancer surgery, supported by evidence from the ENOXACAN II trial and others. However, no guidelines or prospective data exist regarding extended VTE prophylaxis after spinal surgery for metastatic disease, despite comparable or greater VTE risk. A retrospective analysis of 68 consecutive patients who underwent surgery for spinal metastatic disease at UPMC between January 2022 and December 2024 identified a 90-day symptomatic VTE rate of 14.7% (10/68) and a 90-day all-cause mortality rate of 16% (11/68), confirming the high burden of this complication in the local population. This is a single-arm, prospective, open-label interventional pilot study evaluating extended prophylactic anticoagulation with apixaban 2.5 mg orally twice daily for 30 days following hospital discharge. The study population consists of adults (≥18 years) who have undergone spinal surgery for vertebral metastatic disease at UPMC Presbyterian, Shadyside, or Mercy hospitals. Key exclusion criteria include active therapeutic anticoagulation, active bleeding, severe hepatic or renal impairment, concurrent use of strong CYP3A4/P-gp inhibitors or inducers, and inability to discontinue antiplatelet agents or chronic NSAIDs. Apixaban 2.5 mg BID is FDA-approved for VTE prophylaxis following hip replacement (35 days) and knee replacement (12 days). The proposed dose and route are identical to the approved prophylactic regimen. In the ADVANCE-3 trial, apixaban 2.5 mg BID demonstrated superior efficacy to enoxaparin with major bleeding rates of 0.8% vs 0.7%. The AVERT trial demonstrated a 59% reduction in VTE with apixaban 2.5 mg BID in ambulatory cancer patients at intermediate-to-high VTE risk. The primary endpoint is the incidence of symptomatic VTE (DVT and/or PE) within 90 days of hospital discharge. Key secondary endpoints include major bleeding events (ISTH criteria), clinically relevant non-major bleeding events (ISTH criteria), and all-cause mortality at 90 days. Additional secondary endpoints include medication adherence (pill count at Day 31), spinal epidural hematoma requiring intervention, hospital readmission rates, and emergency department visits within 90 days. Follow-up consists of telephone calls at approximately Day 2, Day 31, and Day 91 post-discharge, supplemented by periodic medical record review. No additional clinic visits are required. Outcomes in the prospective cohort (target N=50) will be compared to the historical control cohort (N=68). The primary statistical analysis uses a Bayesian comparison of binomial proportions with a uniform (non-informative) prior distribution. Based on Bayesian power calculations, with 50 enrolled subjects and accounting for an expected 16% attrition from mortality and loss to follow-up (yielding approximately 40-42 evaluable subjects), a 46% reduction in VTE incidence would provide an 85.2% posterior probability of benefit, and a 59% reduction would provide a 92.3% posterior probability of benefit. Stopping rules are pre-specified: enrollment will be paused if ≥2 major bleeding events or ≥4 clinically relevant non-major bleeding events occur. Any single fatal bleeding event or spinal epidural hematoma will trigger immediate safety review. An independent safety monitor provides oversight. This study is conducted under an IND exemption per 21 CFR 312.2(b)(1). Results will inform the design and sample size of a future multicenter randomized controlled trial.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18 years or older * Undergone spinal surgery (any approach) for treatment of vertebral metastatic disease at UPMC Presbyterian, Shadyside, or Mercy Hospital * Planned for discharge to home or acute rehabilitation facility (not hospice) * Willing and able to provide written informed consent * Able to take oral medications * Access to a telephone for follow-up calls Exclusion Criteria: * Already receiving therapeutic anticoagulation for another indication (e.g., atrial fibrillation, prior VTE, mechanical heart valve) * Planned initiation of therapeutic anticoagulation within the next 30 days for another indication * Known allergy or hypersensitivity to apixaban * History of pathological bleeding (e.g., intracranial hemorrhage, gastrointestinal bleeding requiring transfusion or endoscopic intervention within the past 6 months) * Active bleeding at time of planned enrollment * Platelet count less than 50,000/mm³ at time of enrollment * Hemoglobin less than 8 g/dL at time of enrollment * Serum creatinine greater than 2.5 mg/dL * ALT or AST greater than 3 times the upper limit of normal * Total bilirubin greater than 2 times the upper limit of normal * Known severe hepatic impairment (Child-Pugh Class C) * Pregnancy or breastfeeding * Women of childbearing potential unwilling to use adequate contraception during study participation * History of proximal gastrointestinal resection (i.e., gastrectomy and/or proximal small bowel resection) that might alter oral drug absorption * Concurrent use of strong dual inhibitors of CYP3A4 and P-gp or moderate CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin, diltiazem) * Concurrent use of strong dual inducers of CYP3A4 and P-gp (rifampin, carbamazepine, phenytoin, St. John's Wort) * Inability to safely discontinue all antiplatelet medications for the 30-day study drug period, as determined by the treating cardiologist or prescribing physician (aspirin, clopidogrel, ticagrelor) * Inability or unwillingness to discontinue chronic NSAID use during the 30-day study drug period (as-needed use less than 3 days per week is acceptable) * Planned surgery or invasive procedure within the next 30 days * Hospital length of stay 30 days or greater * Prisoner or incarcerated individual * Any other condition that, in the investigator's opinion, would make the subject unsuitable for study participation or unable to comply with study procedures

Outcomes

Primary Outcomes

Incidence of Symptomatic Venous Thromboembolism (VTE)

Number of participants who develop symptomatic deep vein thrombosis (DVT) and/or pulmonary embolism (PE), confirmed by imaging (compression ultrasound, CT pulmonary angiogram, or V/Q scan) or adjudicated by clinical criteria per protocol-defined definitions.

Time frame: Time Frame: Within 90 days of hospital discharge

Secondary Outcomes

Incidence of Major Bleeding Events

Number of participants experiencing major bleeding as defined by International Society on Thrombosis and Haemostasis (ISTH) criteria: fatal bleeding, bleeding in a critical organ, bleeding causing hemoglobin drop ≥2 g/dL, or bleeding requiring transfusion of ≥2 units of packed red blood cells.