There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term ...treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis.
We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan–Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up.
The Kaplan–Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35–0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13–0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42–4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria.
In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan–Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.
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Background & Aims The first studies comparing covered stents (CS) and bare stents (BS) to achieve Transjugular Intrahepatic Portosystemic Shunt (TIPS) were in favor of CS, but only one randomized ...study has been performed. Our aim was to compare the primary patency of TIPS performed with CS and BS. Methods The study was planned as a multicenter, pragmatic (with centers different in size and experience), randomized, single-blinded (with blinding of patients only), parallel group trial. The primary endpoint was TIPS dysfunction defined as either a portocaval gradient ⩾12 mmHg, or a stent lumen stenosis ⩾50%. A transjugular angiography with portosystemic pressure gradient measurement was scheduled every 6 months after TIPS insertion. Results 137 patients were randomized: 66 to receive CS, and 71 BS. Patients who were found to have a hepato-cellular carcinoma, or whose procedure was cancelled were excluded, giving a sample of 129 patients (62 vs. 67). Median follow-up for CS and BS were 23.6 and 21.8 months, respectively. Compared to BS, the risk of TIPS dysfunction with CS was 0.60 95% CI 0.38–0.96, ( p = 0.032). The 2-year rate of shunt dysfunction was 44.0% for CS vs. 63.6% for BS. Early post TIPS complications (22.4% vs. 34.9%), risk of hepatic encephalopathy (0.89 0.53–1.49) and 2-year survival (70% vs. 67.5%) did not differ in the two groups. The 2-year cost/patient was 20 k€ 15.9–27.5 for CS vs. 23.4 k€ 18–37 for BS ( p = 0.52). Conclusions CS provided a significant 39% reduction in dysfunction compared to BS. We did not observe any significant difference with regard to hepatic encephalopathy or death.
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•Phase III, multicenter study, comparing sorafenib + pravastin to sorafenib alone in Child-Pugh A patients with HCC.•The sorafenib-pravastatin combination did not improve overall ...survival in our study population.•Significant prognostic factors for overall survival were CLIP score, performance status, and QoL scores.•In multivariate analysis, only CLIP score was a prognostic factor for overall survival.•The anticancer effect of statins may be more evident in the adjuvant setting, or in the early stages of carcinogenesis.
Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). Combining sorafenib with another treatment, to improve overall survival (OS) within an acceptable safety profile, might be the next step forward in the management of patients with advanced HCC. We aimed to assess whether a combination of sorafenib and a statin improved survival in patients with HCC.
The objective of the PRODIGE-11 trial was to compare the respective clinical outcomes of the sorafenib-pravastatin combination (arm A) versus sorafenib alone (arm B) in patients with advanced HCC. Child-Pugh A patients with advanced HCC who were naive to systemic treatment (n = 323) were randomly assigned to sorafenib-pravastatin combination (n = 162) or sorafenib alone (n = 161). The primary endpoint was OS; secondary endpoints were progression-free survival, time to tumor progression, time to treatment failure, safety, and quality of life.
After randomization, 312 patients received at least 1 dose of study treatment. After a median follow-up of 35 months, 269 patients died (arm A: 135; arm B: 134) with no difference in median OS between treatments arms (10.7 months vs. 10.5 months; hazard ratio = 1.00; p = 0.975); no difference was observed in secondary survival endpoints either. In the univariate analysis, the significant prognostic factors for OS were CLIP score, performance status, and quality of life scores. The multivariate analysis showed that the only prognostic factor for OS was the CLIP score. The main toxicity was diarrhea (which was severe in 11% of patients in arm A, and 8.9% in arm B), while severe nausea-vomiting was rare, and no toxicity-related deaths were reported.
Adding pravastatin to sorafenib did not improve survival in patients with advanced HCC.
Sorafenib has proven efficacy for the treatment of patients with advanced hepatocellular carcinoma. However, overall survival remains poor in these patients, so we were interested to see if the addition of a statin, pravastatin, improved outcomes in patients with advanced HCC. This randomized-controlled trial demonstrated that the sorafenib-pravastatin combination did not improve overall survival in this study population compared to sorafenib alone.
Clinical trial number: NCT01075555.
Aims
To evaluate the diagnostic performance of CT, MRI and CEUS alone and in combination, for the diagnosis of HCC between 10 and 30 mm, in a large population of cirrhotic patients.
Patients and ...methods
In a multicentre prospective trial, 442 patients have been enrolled. Within a month, CEUS, CT and MRI were performed for all patients. A composite algorithm was defined to obtain the more accurate gold standard.
Results
A total of 544 nodules in 381 patients have been retained for the performance analysis. Eighty‐two percent of the patients were male, mean age was 62 years. For the 10‐20 mm nodules (n=342), the sensitivity (Se) and specificity (Sp) for the diagnosis of HCC were, respectively, 70.6% and 83.2% for MRI, 67.9% and 76.8% for CT and 39.6% and 92.9% for CEUS. For the 20‐30 mm nodules (n=202), the Se and Sp were, respectively, 72.3% and 89.4% for MRI, 71.6% and 93.6% for CT and 52.9% and 91.5% for CEUS.
The best combination for the 10‐20 mm nodules was MRI + CT (Se: 55.1%, Sp: 100.0%).
After a first inconclusive technique, CEUS as second image technique allowed the highest specificity with only a slight drop of sensitivity for 10‐20 mm nodules and the highest sensitivity and specificity for 20‐30 mm nodules.
Conclusion
This large multicentre study validates the EASL/AASLD recommendations in daily practice. Specificity using CT or MRI in 10‐20 mm HCC was low, but we do not recommend combined imaging at first as sensitivity would be very low. The best sequential approach combined MRI and CEUS.
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