PIX306 was a phase 3, randomised, single-blind, multicentre trial conducted in adult patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) grade 3 who relapsed after ≥1 rituximab-containing regimen and were not eligible for a stem cell transplant. Patients were randomised 1:1 to pixantrone 50 mg/m2 or gemcitabine 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, combined with rituximab 375 mg/m2 on day 1, for up to six cycles. Patients were followed for up to 96 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), complete response (CR) rate, overall response rate (ORR) and safety. Overall, 312 patients were randomised (median age 73·0 years). The study did not meet its primary endpoint. Median PFS [95% confidence interval (CI)] was 7·3 months (5·2-8·4) with pixantrone + rituximab (PIX + R) and 6·3 months (4·4-8·1) with gemcitabine + rituximab [GEM + R; hazard ratio (HR): 0·85; 95% CI 0·64-1·14; P = 0·28]. Median OS was 13·3 (10·1-19·8) months with PIX + R and 19·6 (12·4-31·9) months with GEM + R (HR: 1·13; 95% CI 0·83-1·53). ORR was 61·9% and 43·9% respectively and CR rate 35·5% and 21·7%. The incidence of adverse events, including cardiac events, was not statistically significant different between PIX + R and GEM + R.

• MeSH
• deoxycytidin analogy a deriváty   farmakologie   terapeutické užití   MeSH
• dospělí MeSH
• isochinoliny farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nehodgkinský lymfom farmakoterapie   patologie   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• rituximab farmakologie   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Angina might persist or reoccur despite successful revascularisation with percutaneous coronary intervention (PCI) and antianginal therapy. Additionally, PCI in stable patients has not been shown to improve survival compared with optimal medical therapy. Trimetazidine is an antianginal agent that improves energy metabolism of the ischaemic myocardium and might improve outcomes and symptoms of patients who recently had a PCI. In this study, we aimed to assess the long-term potential benefits and safety of trimetazidine added to standard evidence-based medical treatment in patients who had a recent successful PCI. METHODS: We did a randomised, double-blind, placebo-controlled, event-driven trial of trimetazidine added to standard background therapy in patients who had undergone successful PCI at 365 centres in 27 countries across Europe, South America, Asia, and north Africa. Eligible patients were aged 21-85 years and had had either elective PCI for stable angina or urgent PCI for unstable angina or non-ST segment elevation myocardial infarction less than 30 days before randomisation. Patients were randomly assigned by an interactive web response system to oral trimetazidine 35 mg modified-release twice daily or matching placebo. Participants, study investigators, and all study staff were masked to treatment allocation. The primary efficacy endpoint was a composite of cardiac death; hospital admission for a cardiac event; recurrence or persistence of angina requiring an addition, switch, or increase of the dose of at least one antianginal drug; or recurrence or persistence of angina requiring a coronary angiography. Efficacy analyses were done according to the intention-to-treat principle. Safety was assessed in all patients who had at least one dose of study drug. This study is registered with the EU Clinical Trials Register (EudraCT 2010-022134-89). FINDINGS: From Sept 17, 2014, to June 15, 2016, 6007 patients were enrolled and randomly assigned to receive either trimetazidine (n=2998) or placebo (n=3009). After a median follow-up of 47·5 months (IQR 42·3-53·3), incidence of primary endpoint events was not significantly different between the trimetazidine group (700 [23·3%] patients) and the placebo group (714 [23·7%]; hazard ratio 0·98 [95% CI 0·88-1·09], p=0·73). When analysed individually, there were no significant differences in the incidence of the components of the primary endpoint between the treatment groups. Similar results were obtained when patients were categorised according to whether they had an elective or urgent PCI. 1219 (40·9%) of 2983 patients in the trimetazidine group and 1230 (41·1%) of 2990 patients in the placebo group had serious treatment-emergent adverse events. Frequencies of adverse events of interest were similar between the groups. INTERPRETATION: Our results show that the routine use of oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice. However, the long-term prescription of this treatment does not appear to be associated with any statistically significant safety concerns in the population studied. FUNDING: Servier.

• MeSH
• aplikace orální MeSH
• bezpečnost MeSH
• hospitalizace statistika a číselné údaje   MeSH
• infarkt myokardu bez ST elevací terapie   MeSH
• koronární angiografie metody   statistika a číselné údaje   MeSH
• koronární angioplastika metody   trendy   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nestabilní angina pectoris terapie   MeSH
• placebo aplikace a dávkování   MeSH
• recidiva MeSH
• senioři MeSH
• smrt MeSH
• stabilní angina pectoris terapie   MeSH
• studie případů a kontrol MeSH
• trimetazidin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• vazodilatancia aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH
• Jižní Amerika MeSH
• severní Afrika MeSH

BACKGROUND: About 30% of angina patients have persisting symptoms despite successful revascularization and antianginal therapy. Moreover, in stable patients, percutaneous coronary intervention (PCI) does not improve survival as compared with medical therapy alone. Trimetazidine, an antianginal agent devoid of hemodynamic effect, may help reducing symptoms and improving outcomes after PCI. The ATPCI study is investigating the efficacy and safety of adding trimetazidine to standard-of-care in angina patients who had a recent PCI. METHODS: ATPCI is a randomized, double-blind, parallel-group, placebo-controlled, event-driven study in patients with coronary artery disease having undergone PCI because of stable angina (elective PCI) or unstable angina/NSTEMI (urgent PCI). After PCI, patients were randomized to trimetazidine (35 mg bid) or placebo on top of standard-of-care including event prevention drugs and antianginal treatment. Patients will be followed for 2 to 4 years. The primary efficacy endpoint is a composite of cardiac death, hospitalization for a cardiac event and recurrence or persistence of angina. Safety events related to trimetazidine use will be monitored. RESULTS: Recruitment lasted from September 2014 to June 2016. A total of 6007 patients were enrolled (58% and 42% after elective and urgent PCI, respectively). Mean age was 61 years, 77% were males, and median durations of coronary artery disease were 1 and 5 months (if urgent or elective PCI, respectively). Almost all patients received drugs for event prevention and antianginal therapy at baseline. CONCLUSION: The ATPCI study will shed further light on the management of contemporary angina patients after PCI. Results are expected in 2019.

• MeSH
• angina pectoris farmakoterapie   chirurgie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• koronární angioplastika * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nemoci koronárních tepen chirurgie   MeSH
• placebo terapeutické užití   MeSH
• pooperační komplikace farmakoterapie   MeSH
• recidiva MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• trimetazidin škodlivé účinky   terapeutické užití   MeSH
• vazodilatancia škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

UNLABELLED: We describe the rationale and design of the ongoing randomized, active-controlled, multicenter, Phase III study evaluating the efficacy of pixantrone and rituximab versus gemcitabine and rituximab in patients with diffuse large B-cell lymphoma or follicular grade 3 lymphoma, who are ineligible for high-dose chemotherapy and stem cell transplantation, and who failed front-line regimens containing rituximab. The administration schedule is pixantrone 50 mg/m(2) intravenously (iv.) or gemcitabine 1000 mg/m(2) iv. on days 1, 8 and 15, combined with rituximab 375 mg/m(2) iv. on day 1, up to six cycles. Pixantrone has a conditional European marketing approval for monotherapy in adults with multiple relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Our trial explores the efficacy of combining pixantrone with rituximab and completes postauthorization measures. TRIAL REGISTRATION NUMBER: NCT01321541.

• MeSH
• deoxycytidin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• dospělí MeSH
• isochinoliny aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• nehodgkinský lymfom farmakoterapie   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři MeSH
• výzkumný projekt MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH