Rivaroxaban vs placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer.

The clinical benefit of extended prophylaxis for venous thromboembolism (VTE) after laparoscopic surgery for cancer is unclear. The efficacy and safety of direct oral anticoagulants for this indication are unexplored. PROphylaxis of venous thromboembolism after LAParoscopic Surgery for colorectal cancer Study II (PROLAPS II) was a randomized, double-blind, placebo-controlled, investigator-initiated, superiority study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban after laparoscopic surgery for colorectal cancer. Consecutive patients who had laparoscopic surgery for colorectal cancer were randomized to receive rivaroxaban (10 mg once daily) or a placebo to be started at 7 ± 2 days after surgery and given for the subsequent 3 weeks. All patients received antithrombotic prophylaxis with low-molecular-weight heparin from surgery to randomization. The primary study outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected deep vein thrombosis (DVT), or VTE-related death at 28 ± 2 days after surgery. The primary safety outcome was major bleeding. Patient recruitment was prematurely closed due to study drug expiry after the inclusion of 582 of the 646 planned patients. A primary study outcome event occurred in 11 of 282 patients in the placebo group compared with 3 of 287 in the rivaroxaban group (3.9 vs 1.0%; odds ratio, 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank P = .032). Major bleeding occurred in none of the patients in the placebo group and 2 patients in the rivaroxaban group (incidence rate 0.7%; 95% CI, 0-1.0). Oral rivaroxaban was more effective than placebo for extended prevention of VTE after laparoscopic surgery for colorectal cancer without an increase in major bleeding. This trial was registered at www.clinicaltrials.gov as #NCT03055026.

Rivaroxaban for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer. Design of the PRO-LAPS II STUDY.

BACKGROUND: The clinical benefit of extending prophylaxis for venous thromboembolism (VTE) beyond hospital discharge after laparoscopic surgery for cancer is undefined. Extended prophylaxis with rivaroxaban is effective in reducing post-operative VTE after major orthopedic surgery without safety concern. METHODS: PROLAPS II is an investigator-initiated, randomized, double-blind study aimed at assessing the efficacy and safety of extended antithrombotic prophylaxis with rivaroxaban compared with placebo after laparoscopic surgery for colorectal cancer in patients who had received antithrombotic prophylaxis with low molecular-weight heparin for 7 ± 2 days (NCT03055026). Patients are randomized to receive rivaroxaban (10 mg once daily) or placebo for 3 weeks (up to day 28 ± 2 from surgery). The primary study outcome is a composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT or VTE-related death at 28 ± 2 days from laparoscopic surgery. The primary safety outcome is major bleeding defined according to the International Society of Thrombosis and Haemostasis. Symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT, major bleeding or death by day 28 ± 2 and by day 90 from surgery are secondary outcomes. Assuming an 8% event rate with placebo and 60% reduction in the primary study outcome with rivaroxaban, 323 patients per group are necessary to show a statistically significant difference between the study groups. DISCUSSION: The PROLAPS II is the first study with an oral anti-Xa agent in cancer surgery. The study has the potential to improve clinical practice by answering the question on the clinical benefit of extending prophylaxis after laparoscopic surgery for colorectal cancer.

Epidemiology and outcome of Clostridium difficile infections in patients hospitalized in Internal Medicine: findings from the nationwide FADOI-PRACTICE study.

BACKGROUND: Clostridium difficile (CD) is a leading cause of diarrhoea among hospitalized patients. The objective of this study was to evaluate the rate, the optimal diagnostic work-up, and outcome of CD infections (CDI) in Internal Medicine (IM) wards in Italy. METHODS: PRACTICE is an observational prospective study, involving 40 IM Units and evaluating all consecutive patients hospitalized during a 4-month period. CDI were defined in case of diarrhoea when both enzyme immunoassay for GDH, and test for A/B toxin were positive. Patients with CDI were followed-up for recurrences for 4 weeks after the end of therapy. RESULTS: Among the 10,780 patients observed, 103 (0.96 %) showed CDI, at admission or during hospitalization. A positive history for CD, antibiotics in the previous 4 weeks, recent hospitalization, female gender and age were significantly associated with CDI (multivariable analysis). In-hospital mortality was 16.5 % in CD group vs 6.7 % in No-CD group (p < 0.001), whereas median length of hospital stay was 16 (IQR = 13) vs 8 (IQR = 8) days (p < 0.001) among patients with or without CDI, respectively. Rate of CD recurrences was 14.6 %. As a post-hoc evaluation, 23 out of 34 GDH+/Tox- samples were toxin positive, when analysed by molecular method (a real-time PCR assay). The overall CD incidence rate was 5.3/10,000 patient-days. CONCLUSIONS: Our results confirm the severity of CDI in medical wards, showing high in-hospital mortality, prolonged hospitalization and frequent short-term recurrences. Further, our survey supports a 2-3 step algorithm for CD diagnosis: EIA for detecting GDH, A and B toxin, followed by a molecular method in case of toxin-negative samples.

Three-month mortality rate and clinical predictors in patients with venous thromboembolism and cancer. Findings from the RIETE registry.

Patients with venous thromboembolism (VTE), and particularly those with cancer, are at increased risk of recurrences, major bleeding, and short- / medium-term mortality. Data from 35,539 patients (6,075 of these with cancer), presenting with symptomatic VTE in the previous three months and enrolled in the worldwide RIETE registry, were evaluated to assess overall and pulmonary embolism (PE)-related mortality, and their potential predictors, with particular focus on patients with cancer. Overall 3-month mortality in the total RIETE population was 7.9%, and death was considered PE-related in 1.4%. Significantly more patients died among those with cancer (26.4%, vs 4.1% in no-cancer group, p<0.001). In 3.0% of cancer patients death was considered PE-related, compared to 1.0% in no-cancer group (p<0.001). Cancer was the strongest independent risk factor for both all-cause and PE-related mortality, and in the subgroup of cancer patients those with advanced disease, reduced mobility, chronic pulmonary disease, and those experiencing PE (vs isolated deep vein thrombosis) were at increased risk of PE-related death. According to the findings of our very large, real-world registry, in the three months following an acute episode VTE remains a substantial cause of mortality. Cancer patients are at particular high risk of VTE-related death. Clinical factors predicting a fatal PE identified in this study (cancer, immobility, comorbidities, increasing age, PE at presentation), could be considered for risk stratification scheme for secondary prophylaxis in daily practice.