Dose-adjusted enoxaparin thromboprophylaxis in hospitalized cancer patients: a randomized, double-blinded multicenter phase 2 trial

Abstract

Hospitalized patients with cancer are at an increased risk of developing venous thromboembolism (VTE). The recommendation for routine pharmacologic thromboprophylaxis in hospitalized patients with cancer to prevent VTE is based on extrapolation of results from noncancer cohorts. There are limited data to support the efficacy and safety of fixed-dose low-molecular-weight heparin (LMWH) regimens in high-risk hospitalized patients with cancer. We conducted a randomized, double-blinded, phase 2 trial in hospitalized patients with active cancer at high risk of developing VTE based on Padua risk score. Patients were randomly assigned to fixed-dose enoxaparin (40 mg daily) vs weight-adjusted enoxaparin (1 mg/kg daily) during hospitalization. The primary objectives were to evaluate the safety of dose-adjusted enoxaparin and evaluate the incidence of VTE with fixed-dose enoxaparin. Blinded clinical assessments were performed at day 14, and patients randomly assigned to fixed-dose enoxaparin subsequently underwent a bilateral lower extremity ultrasound. A total of 50 patients were enrolled and randomized. The median weight of patients enrolled in weight-adjusted enoxaparin arm was 76 kg (range, 60.9-124.5 kg). There were no major hemorrhages or symptomatic VTE in either arm. At time of completion of the blinded clinical assessment, there was only 1 incidentally identified pulmonary embolus that occurred in the weight-adjusted arm. In the group randomly assigned to fixed-dose enoxaparin who subsequently underwent surveillance ultrasound, the cumulative incidence of DVT was 22% (90% binomial confidence interval, 0%-51.3%). This phase 2 trial confirms a high incidence of asymptomatic VTE among high-risk hospitalized patients with cancer and that weight-adjusted LMWH thromboprophylaxis is feasible and well-tolerated. This trial was registered at www.clinicaltrials.gov as #NCT02706249.

Conflict of interest statement

Conflict-of-interest disclosure: J.I.Z. reports receiving research funding from Incyte and Quercegen; consultancy for Sanofi, CSL, and Parexel; and honoraria/advisory boards for Pfizer/BMS, Portola, and Daiichi. A.K.K. reports receiving honoraria from Janssen Pharmaceuticals, Halozyme, Pfizer, Bayer AG, AngioDynamics, and Pharmacyte Biotech; performing a consulting or advisory role for Janssen Pharmaceuticals, Halozyme, Bayer AG, Pfizer, Pharmacyte Biotech, Pharmacyclics, and Seattle Genetics Research; receiving institutional funding from Merck, Array BioPharma, Bristol-Myers Squibb, and Leap Oncology; and receiving funding for travel, accommodations, and expenses from Janssen Pharmaceuticals, Pfizer, and Bayer AG. K.A.B. reports consultancy with Janssen. B.B. reports research funding from Nanoview Bioscience and travel expenses from Erytech Pharma. The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Schema of trial.

Figure 2.

Consort diagram.