High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study.

BACKGROUND: The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain. METHODS: Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or thermal coagulation, and randomized to receive intravenous PPIs according to an intensive regimen (80 mg bolus followed by 8 mg/h as continuous infusion for 72 h) or a standard regimen (40 mg bolus daily followed by saline infusion for 72 h). After the infusion, all patients were given 20 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as ascertained at the repeat endoscopy. RESULTS: Bleeding recurred in 28 of 238 patients (11.8%) receiving the intensive regimen, and in 19 of 236 (8.1%) patients receiving the standard regimen (P= 0.18). Most rebleeding episodes occurred during the initial 72-h infusion: 18 (7.6%) and 19 events (8.1%) in the intensive and standard groups, respectively (P= 0.32). Mean units of blood transfused were 1.7 +/- 2.1 in the intensive and 1.5 +/- 2.1 in the standard regimen group (P= 0.34). The duration of hospital stay was <5 days for 88 (37.0%) and 111 patients (47.0%) in the intensive and standard groups (P= 0.03). There were fewer surgical interventions in the standard versus intensive regimen (1 vs 3). Five patients in each treatment group died. CONCLUSIONS: Following endoscopic hemostasis of bleeding ulcers, standard-dose PPIs infusion was as effective as a high-dose regimen in reducing the risk of recurrent bleeding. (ClinicalTrials.gov number, NCT00374101).

Triple (interferon, ribavirin, amantadine) versus double (interferon, ribavirin) re-therapy for interferon relapser genotype 1b HCV chronic active hepatitis patients.

BACKGROUND: Retreatment for 6 months with the association ribavirin-interferon of HCV-related chronic active hepatitis relapser patients has high probability of failure, mostly in those with genotype 1b. We evaluated the efficacy of extending the therapy from 6 to 12 months without or with the addition of amantadine. METHODS: Forty-nine genotype 1b relapser patients were treated with 3 MU of IFN-alpha2b three times per week and ribavirin 1000-1200 mg daily (double therapy). Twenty-four patients, who did not respond after 6 months of treatment, were randomized to continue for further 6 months either with the same schedule or with also the addition of amantadine 200 mg daily (triple therapy). RESULTS: A sustained virological response was observed in 15/37 subjects (41%) treated for 12 months of double therapy. In the arm of the study evaluating amantadine, end of treatment virologic response was observed in 0/12 patients of double therapy group and in 4/12 of triple therapy (P=0.09). After 6 months of follow-up, a sustained virologic response (SVR) was observed in two patients treated with the triple therapy. CONCLUSIONS: This study confirms poor results of retreatment (even if 12 months double or triple therapy) in relapser patients with HCV hepatitis, genotype 1b. No gain was obtained in prolonging from 6 to 12 months the standard double therapy, while triple therapy with amantadine as an additional regimen for this difficult subgroup of patients showed some cases of SVRs: amantadine addition deserves to be evaluated in larger trials.

From trials to a real hospital setting: effectiveness of pegylated interferon-alpha-2b/ribavirin combination therapy for naïve chronic hepatitis C patients.

Registration trials regarding pegylated interferon treatment of hepatitis C have created great expectations for improved results, but there is little information on actual outcomes in everyday hospital practice. We aimed to define the effectiveness of this treatment in a hospital setting. Seventy-four naïve patients with hepatitis C treated with 12 kD-pegylated-interferon-alpha-2-b/ribavirin (PEG-IFN) were retrospectively analyzed in comparison with 54 patients treated with IFN-alpha-2-b/ribavirin (STANDARD IFN) and with results of three main registration trials. Overall sustained viral response rates were 46% in the STANDARD IFN group and 54% in PEG-IFN group, ranging from 48-61% in similar arms of the registration trials considered, although more of our patients presented comorbidity and high-grade fibrosis, and our dosages at outset of PEG-IFN were lower than optimal (mean 1.18 microg/kg BW). In our hospital setting, the effectiveness of PEG-IFN/ribavirin therapy appeared similar to that reported in large registration trials.