FrancophonIA/ELRC3.0 huggingface dataset:
English: No new safety signals with bevacizumab were observed in study BO21990, but there was a higher incidence of Grade 3 and 4 AEs, SAEs, non-progression deaths, and discontinuations of treatment in the bevacizumab group.
Croatian: Novi sigurnosni signali s bevacizumabom nisu uočeni u ispitivanju BO21990, no prisutna je visoka incidencija 3. i 4. stupnja AE-ova, SAE-ova, neprogresivne smrti i prekida liječenja u grupi koja je primala bevacizumab.
English: In conclusion, as the clinical relevance of the efficacy results is uncertain, and the benefit-risk balance of bevacizumab as an add-on therapy to standard of care for newly diagnosed glioblastoma is considered negative.
Croatian: Zaključno, budući da je klinički značaj rezultata djelotvornosti nesiguran, omjer koristi i rizika za bevacizumab kao dodatne terapije uz standardnu skrb za novodijagnosticirani glioblastom smatra se negativnim.
English: The results of the post hoc analysis according to the RANO criteria were not considered sufficiently robust to resolve the uncertainties around the PFS results.
Croatian: Smatrano je da rezultati post hoc analize prema kriterijima RANO nisu dovoljno čvrsti kako bi se uklonile nesigurnosti vezane uz PFS rezultate.
English: Arterial thromboembolic events, mainly ischaemic strokes, were observed at a slightly higher incidence rate in this trial (5.0%) than in previous bevacizumab trials (up to 3.8% in combination with different chemotherapies), and higher than in the placebo group (1.6%).
Croatian: U ovom ispitivanju uočena je malo viša stopa incidencije arterijskih tromboembolijskih događaja, uglavnom ishemijskih udara, (5,0%) u odnosu na prethodna ispitivanja bevacizumaba (do 3,8% u kombinaciji sa različitim kemoterapijama), te viša u odnosu na grupu koja je uzimala placebo (1,6%).
English: Clinical relevance of PFS: The applicant considered that Avaglio study used a variety of validated and reliable measures to assess the clinical status that captured the patient's perspective (health-related quality of life [HRQOL]), neurocognitive function (Mini Mental Status Examination [MMSE]), and functional status (Karnofsky Performance Status [KPS]).
Croatian: Klinička relevantnost PFS-a: podnositelj zahtjeva smatrao je da ispitivanje Avaglio koristi niz potvrđenih i pouzdanih mjera za ocjenu kliničkog statusa koji omogućuje uvid u perspektivu bolesnika (kvaliteta života povezana sa zdravljem [HRQOL]), neurokognitivnu funkciju (mali pregled mentalnog statusa [MUMSE]), i funkcionalni status (Karnofsky status učinkovitosti [KPS]).
English: Absence of OS benefit: According to the applicant, the use of subsequent lines of therapy, that often included bevacizumab, may have confounded the result.
Croatian: Izostanak koristi OS-a: sukladno tvrdnji podnositelja zahtjeva, primjena naknadnih linija terapije koje često uključuju bevacizumab, može dati pogrešne rezultate.
English: Key post-hoc sensitivity analyses that took into account the concerns raised by the CHMP on the reliability of the imaging technique to detect disease progression excluded patients 1) with potential or confirmed pseudo-progression, 2) with possible pseudo-progression in the Pl+RT/T arm and possible pseudo-response in the Bv+RT/T arm and 3) with PFS < Day 93 to avoid any potential impact of pseudo-progression and post-radiation imaging changes at the first disease assessment.
Croatian: Ključne analize post-hoc osjetljivosti uzele su u obzir zabrinutost koju je iznio CHMP o pouzdanosti tehnike oslikavanja za otkrivanje progresije bolesti, isključujući bolesnike 1) s potencijalnom ili potvrđenom pseudoprogresijom, 2) s mogućom pseudoprogresijom u grupi Pl+RT/T i mogućim pseudo odgovorom u grupi Bv+RT/T te 3) sa PFS-om < dana 93 kako bi se izbjegao mogući učinak na pseudoprogresiju i izgledi za oslikavanje nakon zračenja u prvoj ocjeni bolesti.
English: According to the applicant, the KPS results showed a delay in time to definitive deterioration in KPS in favour of bevacizumab irrespective of whether PD was included (pre-specified) or excluded (exploratory) as an event.
Croatian: Sukladno podnositelju zahtjeva, rezultati KPS-a pokazali su odgodu u vremenu do konačne deterioracije u KPS-u u korist bevacizumaba, bez obzira na to je li PD uključen (prethodno specificirano) ili isključen (eksploratoran) kao događaj.
English: The demonstration of efficacy was based on a randomized, double-blind, placebo controlled, multicenter phase III trial (study BO21990, “AVAglio”) of bevacizumab, temozolomide and radiotherapy (concomitant phase) followed by bevacizumab and temozolomide (maintenance phase) followed by bevacizumab (monotherapy phase) versus placebo, temozolomide (TMZ) and radiotherapy followed by placebo and temozolomide followed by placebo in patients with newly diagnosed glioblastoma (GBM).
Croatian: Dokaz djelotvornosti temeljio se na randomiziranom, dvostruko slijepom, placebo kontroliranom, multicentričnom ispitivanju faze III (ispitivanje BO21990, „AVAglio”) bevacizumaba, temozolomida i radioterapije (kontaminantna faza), nakon čega je slijedila primjena bevacizumaba i temozolomida (faza održavanja), a potom primjena bevacizumaba (monoterapijska faza) u odnosu na placebo, temozolomid (TMZ) i radioterapiju, nakon čega je slijedila primjena placeba i temozolomida, a potom i primjena placeba u bolesnika s novodijagnosticiranim glioblastomom (GBM).
English: The applicant presented his rationale in writing and at an oral explanation.
Croatian: Podnositelj zahtjeva dostavio je svoja pojašnjenja u pisanom i usmenom obliku.
English: Concerning overall survival, the CHMP acknowledged that no OS benefit had been observed in Study BO21990, a finding consistent with the result of the RTOG 0825 trial.
Croatian: Vezano uz cjelokupno preživljenje, CHMP je potvrdio da koristi za OS-a nisu uočene u ispitivanju BO21990, a taj je nalaz konzistentan s rezultatima ispitivanja RTOG 0825.
English: Thus, with the evidence provided, the efficacy of bevacizumab has not been convincingly demonstrated.
Croatian: Stoga djelotvornost bevacizumaba nije uvjerljivo dokazana dostavljenim dokazima.
English: Study methodology including imaging and disease assessment criteria: The applicant considered that the pivotal study (Avaglio) was designed using standard methodology in GBM for the assessment of tumour growth and followed the current clinical practice.
Croatian: Metodologija ispitivanja, uključujući oslikavanje i kriterije ocjene bolesti: podnositelj zahtjeva ocijenio je da je pivotalno ispitivanje (Avaglio) dizajnirano primjenom standardne metodologije u GBM-u za ocjenu rasta tumora te da se pridržavalo aktualne kliničke prakse.
English: The observed efficacy results in study BO21990 were overall consistent with the results reported from another trial investigating the effect of bevacizumab in glioblastoma (RTOG0825), i.e., no effect on OS, no benefit in terms of HRQoL, and possibly even a detriment in neurocognitive functioning (as suggested in study RTOG0825).
Croatian: Rezultati uočene djelotvornosti u BO21990 bili su načelno konzistentni s rezultatima prijavljenima u drugom ispitivanju, kojim se ispitivalo djelovanje bevacizumaba u slučaju glioblastoma (RTOG0825), odnosno izostanak djelovanja na OS, izostanak koristi u smislu HRQoL, a moguće čak i gubitak neurokognitivne funkcije (kako je predloženo u ispitivanju RTOG0825).
English: The analysis OS showed no statistically significant difference in survival time between the bevacizumab arm and the placebo arm (HR 0.89, 95% CI 0.75-1.07, p=0.2135).
Croatian: Analizom OS-a nisu dokazane nikakve statistički značajne razlike u vremenu preživljenja između grupe koja je uzimala bevacizumab i grupe koja je uzimala placebo (HR 0,89, 95% CI 0,75-1.07, p=0,2135).
English: The SAG also commented on the long survival observed for numerous patients with early progression and concluded that this finding was counterintuitive and possibly a further indication of the lack of clinical meaningfulness of the PFS adjudication criteria used in the study.
Croatian: SAG je također komentirao dugo preživljenje koje je uočeno za veliki broj bolesnika s ranom progresijom i zaključio je da su dotični nalazi kontraintuitivni, te da je moguća daljnja indikacija manjka značajnosti kriterija indikacije PFS-a primijenjenog u ispitivanju.
English: The applicant did not convincingly show that the sensitivity analyses performed were able to mitigate the risk of systematic biases in the evaluation of PFS and were adequate to provide sufficient reassurance that bevacizumab produces a PFS increase of clinically important magnitude.
Croatian: Podnositelj zahtjeva nije uvjerljivo dokazao da su provedene analize osjetljivosti uspješno umanjile rizik sistematskih pristranosti u ocjeni PFS-a, te da su primjerene za pružanje dovoljno pouzdanosti da bevacizumab proizvodi povećanje PFS-a od kliničkog značaja.
English: Several strategies were applied prospectively in Avaglio in order to minimize the possibility of incorrectly interpreting the MRI scan including implementation of an algorithm for the determination of pseudo-progression.
Croatian: Nekoliko je kriterija primijenjeno prospektivno u ispitivanju lijeka Avaglio kako bi se smanjila mogućnost neispravnog tumačenja slike magnetske rezonancije, uključujući i primjenu algoritama za utvrđivanje pseudoprogresije.
English: Overall the conclusion on the efficacy of bevacizumab in this setting was that the clinical relevance of the observed effect on PFS cannot be determined and that a relevant effect has not been established on the basis of any other clinical relevant endpoint.
Croatian: Cjelokupan zaključak o djelovanju bevacizumaba u ovom okruženju glasio je da se klinička relevantnost uočenog djelovanja PFS-a ne može utvrditi te da nije utvrđeno relevantno djelovanje na temelju bilo kojih drugih klinički relevantnih završnih točaka.
English: Following the CHMP scientific conclusions adopted in 22 May 2014 that Avastin was not approvable in combination with radiotherapy and temozolomide for the treatment of adult patients with newly diagnosed glioblastoma on the basis of the following grounds for the refusal of the Marketing Authorisation:
Croatian: Nakon znanstvenih zaključaka CHMP-a usvojenih 22. svibnja 2014. godine da se Avastin ne može odobriti u kombinaciji s radioterapijom i temozolomidom za liječenje odraslih bolesnika s novodijagnosticiranim glioblastomom na temelju sljedećih razloga za odbijanje odobrenja za stavljanje lijeka u promet:
English: Overall summary of the scientific evaluation
Croatian: Cjelokupan sažetak znanstvenog zaključka
English: Thus, the CHMP maintained the view that it was not possible to estimate with sufficient confidence the magnitude of the gain in tumour control provided by bevacizumab when added to standard of care.
Croatian: Stoga CHMP zadržava stav da nije moguće ocijeniti s dostatnom pouzdanošću razmjer koristi za kontrolu tumora koju omogućuje bevacizumab u slučaju kada se dodaje standardnoj skrbi.
English: The MAH for Avastin applied for an extension of indication to include Avastin in combination with radiotherapy and temozolomide for the treatment of adult patients with newly diagnosed glioblastoma.
Croatian: Nositelj odobrenja za lijek Avastin prijavio je proširenje indikacije kako bi uključio Avastin u kombinaciju radioterapije i temozolomida za liječenje odraslih bolesnika s novodijagnosticiranim glioblastomom.
English: Therefore, the CHMP has recommended the refusal of the variation of the marketing authorisation for Avastin in the treatment of adult patients with newly diagnosed glioblastoma in combination with radiotherapy and temozolomide.
Croatian: Stoga je CHMP preporučio odbijanje izmjene odobrenja za stavljanje u promet lijeka Avastin za liječenje odraslih bolesnika s novodijagnosticiranim glioblastomom u kombinaciji s radioterapijom i temozolomidom.
English: The main efficacy issue was about the clinical relevance of the radiological endpoint PFS in the absence of a clinically relevant effect on OS. Antiangiogenic agents, especially those targeting vascular endothelial growth factor (VEGF), such as bevacizumab, can produce marked decrease in contrast enhancement and commonly result in high radiologic response rates.
Croatian: Antiangiogenski lijekovi, posebice oni čiji je cilj djelovanje na krvožilni endotelijalni čimbenik rasta (VEGF), poput bevacizumaba, može proizvesti markirano smanjenje u pojačanju kontrasta i općenito rezultirati visokim stopama radiološkog odgovora.
English: The analysis OS showed no statistically significant difference in survival time between the bevacizumab arm and the placebo arm. Arguably, one-way cross-over after progression may hamper the detection of a difference in OS.
Croatian: Analiza OS-a pokazala je da nema statistički značajne razlike u vremenu preživljenja između grupe koja je primala bevacizumab i grupe koja je primala placebo.
English: Therefore, the CHMP concluded on 22 May 2014 that the benefit/risk ratio of bevacizumab in combination with radiotherapy and temozolomide for the treatment of adult patients with newly diagnosed glioblastoma was negative.
Croatian: Stoga je CHMP zaključio 22. svibnja 2014. da je omjer koristi i rizika za bevacizumab u kombinaciji s radioterapijom i temozolomidom za liječenje odraslih bolesnika s novodijagnosticiranim glioblastomom negativan.
English: • Safety issues
Croatian: • Pitanje sigurne primjene
English: While the applicant acknowledged that there is an on-going evolution of the criteria used to assess disease progression in brain tumours, they contended that the criteria used in Avaglio study represent the most advanced and accepted technology in line with expert recommendations.
Croatian: Budući da podnositelj zahtjeva raspolaže znanjem o kontinuiranoj evoluciji kriterija korištenih za ocjenu progresije bolesti u tumora na mozgu, argumentirali su da kriteriji primijenjeni u ispitivanju
English: 60 minutes later.
Croatian: 60 minuta kasnije.
English: Although they are rare, the symptoms can be severe.
Croatian: Iako su rijetki, ovi simptomi mogu biti teški.
English: ()) every 3 or 4 days for 12 weeks.
Croatian: (*)) svaka 3 ili 4 dana tijekom 12 tjedana.
English: Adults and adolescents (12 years and above)
Croatian: Odrasli i adolescenti (12 godina i stariji)
English: Currently available data are described in sections 4.8, 5.1, and 5.2.
Croatian: Trenutno dostupni podaci opisani su u dijelovima 4.8, 5.1. i 5.2.
English: • voice-box (larynx), which may make breathing difficult
Croatian: • grkljana (larinksa), što može otežati disanje
English: Your doctor will discuss with you the risks and benefits of taking this medicine.
Croatian: Liječnik će s Vama razgovarati o rizicima i koristima uzimanja ovog lijeka.
English: This can include allergic-type reactions.
Croatian: To može uključivati reakcije alergijskog tipa.
English: • face, eyelids, lips or tongue
Croatian: • lica, vjeđa, usana ili jezika
English: If you are injecting Cinryze yourself, always use it exactly as your doctor has instructed you.
Croatian: Ako sami sebi ubrizgavate Cinryze, uvijek ga primijenite točno onako kako Vam je rekao liječnik.
English: Make sure all the powder is completely dissolved.
Croatian: Pazite da se sav prašak potpuno otopi.
English: B - 1000 Brussels Belgium medinfoeuceemea@shire.com
Croatian: B - 1000 Brussels Belgija medinfoeuceemea@shire.com
English: Prevention:
Croatian: Prevencija:
English: Therefore, Cinryze should be given to pregnant women only if clearly indicated.
Croatian: Stoga se Cinryze smije davati trudnicama samo ako postoji jasna indikacija.
English: You will be carefully monitored if this is the case.
Croatian: U tom će Vas slučaju pažljivo nadzirati.
English: You or your carer might also administer Cinryze as an injection, but only after receiving adequate training.
Croatian: I Vi ili Vaš njegovatelj također možete primijeniti Cinryze kao injekciju, ali samo nakon što ste dobili odgovarajuću obuku.
English: Tell your doctor immediately if you experience any of the following symptoms after taking this medicine.
Croatian: Odmah obavijestite svog liječnika ako osjetite neki od sljedećih simptoma nakon uzimanja ovog lijeka.
English: None of these adverse reactions were severe, and none led to discontinuation of medicinal product.
Croatian: Nijedna od ovih nuspojava nije bila teška i nijedna nije dovela do prekida primjene lijeka.
English: Two additional studies evaluated plasma levels in children (6-11 years).
Croatian: Dva dodatna ispitivanja procijenila su razine u plazmi u djece (6-11 godina).
English: Date of first authorisation: 15 June 2011 Date of latest renewal: 26 May 2016
Croatian: Datum posljednje obnove: 26. svibnja 2016.
English: Data supporting dosing recommendations in children less than 6 years old are very limited.
Croatian: Podaci u korist preporuka o doziranju u djece mlađe od 6 godina vrlo su ograničeni.
English: Local reactions at the injection site were uncommon.
Croatian: Lokalne reakcije na mjestu injekcije bile su manje česte.
English: Hypersensitivity reactions may have symptoms similar to angioedema attacks.
Croatian: Reakcije preosjetljivosti mogu imati simptome slične napadajima angioedema.
English: Indication for treatment (acute attack or prophylaxis) Response to treatment
Croatian: Indikaciju za liječenje (akutni napadaj ili profilaksa) Odgovor na liječenje
English: • hands and feet
Croatian: • šaka i stopala
English: It is important to tell your doctor if you think you have ever had an allergic reaction to any of the ingredients in Cinryze.
Croatian: Važno je da obavijestite svog liječnika ako mislite da ste ikad prije imali alergijsku reakciju na bilo koji sastojak lijeka Cinryze.
English: Non-clinical data reveal no special hazard for humans based on conventional studies of general toxicity and toxicity to reproduction.
Croatian: Neklinički podaci ne ukazuju na poseban rizik za ljude na temelju konvencionalnih ispitivanja opće toksičnosti i reproduktivne toksičnosti.
English: The main function of serpins is to regulate the activity of serine proteases.
Croatian: Glavna funkcija serpina je regulacija aktivnosti serinskih proteaza.
English: Other medicines and Cinryze
Croatian: Drugi lijekovi i Cinryze
English: What Cinryze is and what it is used for
Croatian: Što je Cinryze i za što se koristi
English: For 95% of attacks, clinical relief was observed and/or subjects were discharged to home within 4 hours.
Croatian: U 95% napadaja bilo je opaženo kliničko olakšanje i/ili su ispitanici bili otpušteni kući u roku od 4 sata.
English: The safety and efficacy of Cinryze in children less than 2 years old has not been established.
Croatian: Sigurnost i djelotvornost lijeka Cinryze u djece mlađe od 2 godine nisu ustanovljene.
English: Based upon an animal study there is a potential thrombogenic threshold at doses greater than 200 Units
Croatian: Na temelju ispitivanja u životinja postoji mogući trombogeni prag pri dozama većima od 200 jedinica
English: Cinryze based on body weight (see section 5.1).
Croatian: Cinryze na temelju tjelesne težine (vidjeti dio 5.1).
English: 1077 XX Amsterdam The Netherlands
Croatian: 1077 XX Amsterdam Nizozemska
English: Parameters
Croatian: Parametri
English: Technique of intravenous injection
Croatian: Tehnika intravenske injekcije
English: Like all medicines, Cinryze can cause side effects, although not everybody gets them.
Croatian: Kao i svi lijekovi, Cinryze može uzrokovati nuspojave iako se one neće javiti kod svakoga.
English: Patients with known risk factors for thrombotic events (including indwelling catheters) should be monitored closely.
Croatian: Bolesnike s poznatim čimbenicima rizika za trombotičke događaje (uključujući trajne katetere) treba pažljivo pratiti.
English: • Before you start treatment with Cinryze, it is important that you tell your doctor if you have, or have had, problems with your blood clotting (thrombotic events).
Croatian: • Prije početka liječenja lijekom Cinryze važno je da obavijestite svog liječnika ako imate ili ste imali tegobe sa zgrušavanjem krvi (trombotičke događaje).
English: What you need to know before you take Cinryze
Croatian: Što morate znati prije nego počnete uzimati Cinryze
English: n= number of subjects evaluated.
Croatian: n= broj ocijenjenih ispitanika
English: In case of anaphylactic reactions or shock, emergency medical treatment should be administered.
Croatian: U slučaju anafilaktičkih reakcija ili šoka potrebno je primijeniti hitno medicinsko liječenje.
English: Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), and not known (cannot be estimated from the available data).
Croatian: Učestalost se definira kao vrlo često (≥1/10), često (≥1/100 i <1/10), manje često (≥1/1000 i <1/100), rijetko (≥1/10 000 i <1/1000), vrlo rijetko (<1/10 000) i nepoznato (ne može se procijeniti iz dostupnih podataka).
English: Among reports of venous thrombosis, the most common underlying risk factor was presence of an indwelling catheter.
Croatian: Među prijavljenim slučajevima venske tromboze najčešći osnovni čimbenik rizika bila je prisutnost uvedenog trajnog katetera.
English: What Cinryze is and what it is used for What you need to know before you take Cinryze How to take Cinryze
Croatian: Što je Cinryze i za što se koristi Što morate znati prije nego počnete uzimati Cinryze Kako uzimati Cinryze
English: * Historically assigned potency values are expressed in in-house Units (U).
Croatian: *Povijesno dodijeljene vrijednosti za jačinu izražene su u jedinicama (U) ustanove.
English: What Cinryze looks like and contents of the pack
Croatian: Kako Cinryze izgleda i sadržaj pakiranja
English: If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking Cinryze.
Croatian: Ako ste trudni ili dojite, mislite da biste mogli biti trudni ili planirate imati dijete, obratite se svom liječniku za savjet prije nego uzmete Cinryze.
English: Single Dose (1000 Units*)
Croatian: Jedna doza (1000 jedinica*)
English: • If you are allergic to C1 inhibitor or any of the other ingredients of Cinryze (listed in section 6).
Croatian: • ako ste alergični na inhibitor C1 ili neki drugi sastojak lijeka Cinryze (naveden u dijelu 6).
English: The maximum serum concentration (Cmax) and area under the serum concentration-time curve (AUC) appeared to increase from the single to double dose, although the increase was not dose-proportional.
Croatian: Činilo se da su se najviša koncentracija u serumu (Cmax) i površina ispod krivulje koncentracija-vrijeme (AUC) povećale od jednostruke do dvostruke doze, iako to povećanje nije bilo proporcionalno dozi.
English: Both doses resulted in similar reduction of attack-frequency and showed clinical benefit regarding severity, duration, and requirement for acute treatment of attacks.
Croatian: Obje doze dovele su do sličnog smanjenja učestalosti napadaja i pokazale kliničku korist što se tiče težine, trajanja i zahtjeva za akutno liječenje napadaja.
English: 2 protective mats
Croatian: 2 zaštitne podloge
English: A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Cinryze therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Croatian: Potrebno je odlučiti da li prekinuti dojenje ili prekinuti liječenje/suzdržati se od liječenja lijekom Cinryze uzimajući u obzir korist dojenja za dijete i korist liječenja za ženu.
English: If your doctor decides that you may be suitable for such home-treatment, he/she will give you detailed instructions.
Croatian: Ako liječnik odluči da ste pogodni za takvo liječenje kod kuće, dat će Vam detaljne upute.
English: If these symptoms occur after administration, they should alert their physician.
Croatian: Ako se ovi simptomi pojave nakon primjene, bolesnici moraju upozoriti svog liječnika.
English: However, chemical and physical in-use stability has been demonstrated for 3 hours at room temperature (15C - 25C).
Croatian: Međutim, dokazana je kemijska i fizikalna stabilnost rekonstituiranog lijeka u trajanju od 3 sata na sobnoj temperaturi (15C - 25C).