qanastek/EMEA-V3 huggingface dataset:
Xigris should be used within 48 hours of the start of organ failure and is best used when treatment can be started within 24 hours after the start of organ failure.
Xigris għandu jintuża fi żmien 48 siegħa minn meta l- organi ma jibqgħux jaħdmu sew u huwa wżat l- aħjar meta t - trattament jista ’ jinbeda fi żmien 24 siegħa minn meta l- organi ma jibqgħux jaħdmu sew.
Xigris should not be used in children.
Xigris m’ għandux jintuża fit- tfal.
How does Xigris work?
Kif jaħdem Xigris?
Excessive blood clotting is a problem during severe sepsis, when the blood clots can block the blood supply to important parts of the body such as the kidneys and lungs.
Tgħaqqid eċċessiv tad- demm huwa problema waqt sepsis serja, meta l- emboli tad- demm jistgħu jostakolaw il- provvista tad- demm fil- partijiet importanti tal- ġisem bħalma huma l- kliewi u l- pulmun.
Xigris is an anticoagulant, which prevents coagulation (clotting).
Xigris huwa antikoagulant, li jipprevjeni l- koagulazzjoni (tgħaqqid tad- demm).
The active ingredient of Xigris is drotrecogin alfa (activated), which is very similar to a natural anticoagulant found in the body called activated protein C.
Is- sustanza attiva ta ’ Xigris hija drotrecogin alfa (attivata), li hija simili ħafna għal antikoagulant naturali li jinstab fil- ġisem imsejjaħ proteina Ċ attivata.
Drotrecogin alfa (activated), is produced by a method known as ‘ recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce it.
Drotrecogin alfa (attivata), hija magħmula permezz ta ’ metodu magħruf bħala ‘ teknoloġija rikombinanti tad- DNA ’: hija magħmula minn ċellola li tkun irċiviet ġene (DNA), li jagħmilha kapaċi tipproduċiha.
In the body, drotrecogin alfa limits how much thrombin (one of the factors involved in blood clotting) is produced, and also reduces the inflammation caused by the infection.
Fil- ġisem, drotrecogin alfa tillimita l- produzzjoni ta ’ thrombin (wieħed
(44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged How has Xigris been studied?
Bl- użu ta ’ Xigris waqt sepsis, ir- riskju li jifformaw emboli tad- demm jitnaqqas.
The effectiveness of Xigris in severe sepsis has been studied in two studies.
L- effettività ta ’ Xigris f’ sepsis serja ġiet studjata f’ żewġ studji.
In the PROWESS study, Xigris was compared to placebo (dummy treatment) in 1,690 patients.
Fl- istudju PROWESS, Xigris tqabbel ma ’ plaċebo (trattament finta) f’ 1, 690 pazjent.
In the ENHANCE study, over 2,000 patients received Xigris.
Fl- istudju ENHANCE, aktar minn 2, 000 pazjent irċievew Xigris.
One study (ADDRESS) was carried out in patients with severe sepsis with a lower risk of death (almost 3,000 patients, comparison to placebo).
Sar studju (ADDRESS) fuq pazjenti b’ sepsis serja b’ riskju aktar baxx ta ’ mewt (kważi 3, 000 pazjent, tqabbil ma ’ plaċebo).
All the studies looked at the reduction in death seen at 28 days.
L- istudji kollha studjaw it- tnaqqis fl- ammont ta ’ mewt muri fit- 28 jum.
What benefit has Xigris shown during the studies?
X’ benefiċċju wera Xigris waqt l- istudji?
Fewer patients treated with Xigris had died at 28 days than patients treated with a placebo.
Inqas pazjenti trattati b’ Xigris mietu fit- 28 jum milli pazjenti ittrattati bi plaċebo.
This was more marked when Xigris was given within 24 hours of the start of organ failure, and in patients who had more than one organ failure.
Dan deher b’ mod aktar ċar meta Xigris ingħata fi żmien 24 siegħa minn meta l- organi ma baqgħux jaħdmu sew, u f’ pazjenti li kellhom ħsara f’ aktar minn organu wieħed.
The results suggest that Xigris is best given early after the start of organ failure and it is therefore recommended that Xigris be given within 24 hours of the onset of the organ failure.
Ir- riżultati jissuġġerixxu li Xigris l- aħjar jingħata fi żmien 24 siegħa minn meta l- organi ma jibqgħux jaħdmu sew.
What is the risk associated with Xigris?
X’ inhu r- riskju assoċjat ma ’ Xigris?
As with other anticoagulants, the most common side effect of Xigris is bleeding.
Bħal b’ antikoagulanti oħra, l- aktar effett sekondarju komuni ta ’ Xigris huwa fsada.
For the full list of all side effects reported with Xigris, see the Package Leaflet.
Għal- lista sħiħa ta ’ l- effetti sekondarji kollha irrapportati b’ Xigris, ara l- Fuljett ta ’ Tagħrif.
Xigris should not be used in people who may be hypersensitive (allergic) to drotrecogin alfa (activated), any of the other ingredients or bovine thrombin (a cow protein), or in patients who have long-term liver disease or a brain tumour.
Xigris m’ għandux jintuża f’ nies li jistgħu jkunu sensittivi żżejjed (allerġiċi) għal drotrecogin alfa (attivata), jew għal xi sustanzi attivi jew thrombin bovin (proteina tal- baqra), jew f’ pazjenti b’ mard tal- fwied fuq tul ta ’ żmien jew b’ tumur tal- moħħ.
Xigris should not be used in patients with any current bleeding or risk of bleeding (see the Package Leaflet for the full list of restrictions), and doctors must be careful when using Xigris at the same time as other anticoagulant medicines (such as warfarin or high-dose heparin) – the full list is available in the Summary of Product Characteristics (also part of the EPAR).
Xigris m’ għandux jintuża f’ pazjenti bi xi fsada kurrenti jew riskju ta ’ fsada (ara l- Fuljett ta ’ Tagħrif għal- lista sħiħa ta ’ restrizzjonijiet), u t- tobba jeħtieġ li joqgħodu attenti meta jużaw Xigris fl- istess waqt ma ’ mediċini antikoagulanti oħra (bħal warfarina jew ħeparina b’ doża għolja) – il- lista sħiħa hija disponibbli fis- Sommarju tal- Karatteristiċi tal- Prodott (ukoll parti mill- EPAR)
Why has Xigris been approved?
Għal x’ hiex ġie approvat Xigris?
The Committee for Medicinal Products for Human Use (CHMP) decided that Xigris’ s benefits are greater than its risks for patients with severe sepsis and multiple organ failure.
Il- Kumitat għal Prodotti Mediċinali għal Użu Uman (CHMP) iddeċieda li l- benefiċċji ta ’ Xigris huma akbar mir- riskji tiegħu għal pazjenti b’ sepsis serja u bi ħsara f’ aktar minn organu wieħed.
The Committee recommended that Xigris be given marketing authorisation.
Il- Kumitat irrakkomanda li Xigris jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Xigris has been authorised under "Exceptional Circumstances".
Xigris ġie awtorizzat taħt “ Ċirkostanzi ta ’ Eċċezzjoni ”.
This means that it has not been possible to obtain complete information about Xigris..
Dan ifisser li ma kienx possibbli li jinkiseb tagħrif sħiħ dwar Xigris.
Every year, the European Medicines Agency (EMEA) will review any new information that may become available and this summary will be updated as necessary.
Kull sena, l- Aġenzija Ewropea għall- Mediċini (EMEA) għandha tirrevedi kwalunkwe tagħrif ġdid li jista ’ jsir disponibbli u dan is- Sommarju għandu jkun aġġornat kif meħtieġ.
What information is still awaited for Xigris?
X’ tagħrif għadu mistenni għal Xigris?
The company that makes Xigris will conduct an additional study looking at the safety and effectiveness of Xigris in patients with severe sepsis.
Il- kumpanija li tagħmel Xigris se tagħmel studju addizzjonali li se jistudja s- sigurtà u l- effettività ta ’ Xigris f’ pazjenti b’ sepsis serja.
Other information about Xigris:
Tagħrif ieħor dwar Xigris:
The European Commission granted a marketing authorisation valid throughout the European Union for Xigris to Eli Lilly Nederland B. V. on 22 August 2002.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Xigris lil Eli Lilly Nederland B. V. fit- 22 ta ’ Awwissu 2002.
The marketing authorisation was renewed on 22 August 2007.
L- awtorizzazzjoni għat - tqegħid fis- suq ġiet imġedda fit- 22 ta ’ Awwissu 2007.
The full EPAR for Xigris is available here.
L- EPAR sħiħ għal Xigris huwa disponibbli minn hawnhekk.
Xigris 20 mg powder for solution for infusion
Xigris 20 mg trab għal soluzzjoni għall- infużjoni
Each vial contains 20 mg of Drotrecogin alfa (activated).
Kull kunjett fih 20 mg ta ’ Drotrecogin alfa (attivat)
After reconstitution with 10 ml of Water for Injection each ml contains 2 mg of Drotrecogin alfa (activated).
Wara r- rikostituzzjoni b’ 10 ml ta ’ Ilma għall- Injezzjonijiet kull ml fih 2 mg ta ’ Drotrecogin alfa.
Drotrecogin alfa (activated) is a recombinant version of the endogenous activated Protein C and is produced by genetic engineering from an established human cell line.
Drotrecogin alfa (attivat) huwa tip rikombinat tal- Proteina Ċ attivata b’ mod endoġenu li huwa magħmul b’ inġinerija ġenetika minn razza stabbilita ta ’ ċelloli umani.
For a full list of excipients, see 6.1.
Kull kunjett fih madwar 68 mg ta ’ sodium. Għal lista kompleta ta ’ sustanzi mhux attivi, ara Sezzjoni 6. 1.
Xigris is supplied as a lyophilised, white to off-white powder.
Xigris issibu bħala trab lijofilizzat ta ’ kulur abjad fil- griż jew abjad.
Xigris is indicated for the treatment of adult patients with severe sepsis with multiple organ failure when added to best standard care.
Xigris huwa indikat għal kura ta ’ pazjenti adulti b’ sepsis gravi b’ indeboliment ta ’ organi multipli, meta jingħata ma ’ l- aħjar kura standardizzata.
The use of Xigris should be considered mainly in situations when therapy can be started within 24 hours after the onset of organ failure (for further information see section 5.1).
L- iżjed sitwazzjonijiet fejn għandu jiġi kkunsidrat l- użu ta ’ Xigris huma meta t- terapija tista ’ tingħata fi żmien 24 siegħa minn meta beda l- indeboliment ta ’ l - organi. (għal aktar tagħrif ara sezzjoni 5. 1).
Xigris should be used by experienced doctors in institutions skilled in the care of patients with severe sepsis.
Xigris għandu jintuża minn tobba ta ’ esperjenza li jkunu mħarrġa f’ istituzzjonijiet għall- kura ta’ pazjenti b’ sepsis gravi.
Treatment should be started within 48 hours, and preferably within 24 hours, of onset of the first documented sepsis-induced organ dysfunction (see section 5.1).
Il- kura għandha tibda fi żmien 48 siegħa, u preferibilment fi żmien 24 siegħa, mill- ewwel sinjali dokumentati ta ’ nuqqas ta ’ funzjoni ta ’ l- organi minħabba s- sepsis (ara sezzjoni 5. 1).
The recommended dose of Xigris is 24 µg/ kg/ hr (based on actual body weight) given as a continuous intravenous infusion for a total duration of 96 hours.
Id- doża rakkomandata ta ’ Xigris hi ta ’ 24µg/ kg/ siegħa (ibbażat fuq il- piż tal- ġisem attwali) li jingħataw bħala infużjoni kontinwa fil- vina għal perjodu totali ta ’ 96 siegħa.
It is recommended that Xigris be infused with an infusion pump to accurately control the infusion rate.
Hu rakkomandat li l - infużjoni ta ’ Xigris issir permezz ta ’ pompa biex ir- rata ta ’ l- infużjoni tkun ikkontrollata tajjeb.
If the infusion is interrupted for any reason, Xigris should be restarted at the 24 µg/ kg/ hr infusion rate and continued to complete the full recommended 96 hours of dosing administration.
Jekk l - infużjoni titwaqqaf għal xi raġuni, Xigris għandu jerġa ’ jibda jingħata bir- rata ta ’ 24µg/ kg/ siegħa u jitkompla sakemm tintlaħaq id- doża sħiħa rakkomandata ta ’ 96 siegħa.
Dose escalation or bolus doses of Xigris are not necessary to account for the interruption in the infusion.
Mhux meħtieġ li tiżdied id - doża jew li jingħataw dożi bolus ta ’ Xigris biex jagħmlu tajjeb għall- waqfa fl- infużjoni.
No dose adjustments are required in adult patients with severe sepsis with regard to age, gender, hepatic function (as measured by transaminase levels), renal function, obesity or co-administration of prophylactic heparin.
Mhux meħtieġ tibdil fid- doża għal pazjenti adulti b’ sepsis gravi għal dik li hi età, sess, il- funzjoni tal - fwied (imkejla skond il- livelli transaminażi), il- funzjoni renali, l- obeżità jew it- teħid fl- istess żmien ma ’ eparina mgħotija għal skop profilattiku.
The pharmacokinetics of drotrecogin alfa (activated) have not been studied in patients with severe sepsis and pre-existing end stage renal disease and chronic hepatic disease.
Il- farmakokinetika ta ’ drotrecogin alfa (attivat) ma ġietx studjata fil- pazjenti b’ sepsis gravi li jkunu jbatu b’ mard terminali tal- kliewi jew b’ mard kroniku tal - fwied.
Paediatrics:
2 Pazjenti f’ età pedjatrika:
Data from a placebo-controlled clinical trial which was stopped for futility after 477 patients 0 to 17 years-old had received the study treatment did not establish efficacy of Xigris in
Skond l- informazzjoni li ħarġet minn studju kliniċi kkontrollati bi plaċebo, li twaqqfu minħabba l- inutilità wara li 477 pazjent bejn it- twelid u s- 17- il sena kienu ngħataw il- kura għal skopijiet ta ’ studju, instab li Xigris ma kinitx effikaċi f’ pazjenti żgħar, u wriet li dawk li ħadu Xigris kellhom rata ogħla ta ’ fsada fis- sistema nervuża ċentrali minn dawk li ħadu l- plaċebo.
Therefore no dosage recommendation can be made and the use of Xigris is not recommended in children below the age of 18 (see section 4.4).
Għalhekk ma tistax issir rakkomandazzjoni dwar id- doża u l- użu ta ’ Xigris mhuwiex rakkomandat għal tfal taħt it- 18- il sena (ara sezzjoni 4. 4).
Hypersensitivity to the active substance, to any of the excipients or to bovine thrombin (a trace residue from the manufacturing process).
Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi jew għal trombin bovina (traċċa ta ’ residwu mill- proċess tal- manifattura).
• Active internal bleeding • Patients with intracranial pathology; neoplasm or evidence of cerebral herniation • Concurrent heparin therapy ≥ 15 International Units/ kg/ hr • Known bleeding diathesis except for acute coagulopathy related to sepsis • Chronic severe hepatic disease • Platelet count < 30,000 x 106/ l, even if the platelet count is increased after transfusions • Patients at increased risk for bleeding (for example):
Minħabba li drotrecogin alfa (attivat) jista ’ jżid ir- riskju ta ’ fsada, Xigris m’ għandux jintuża f’ dawn iċ - ċirkostanzi: • Fsada interna u attiva • Pazjenti b’ patoloġija intrakranika; neoplażma jew evidenza ta ’ ernja ċerebrali • Terapija bl- eparina fl- istess żmien ≥ 15- il Unità Internazzjonali/ kg/ siegħa • Dijateżi magħrufa tal- fsada, ħlief għal koagulopatija akuta relatata mas- sepsis • Mard gravi u kroniku tal- fwied Għadd tal- plejtlets < 30, 000 x 106/ 1, ukoll jekk l- għadd tal- plejtlets jiżdied wara t- trasfużjonijiet • • Pazjenti li jkollhom riskju akbar ta ’ fsada (per eżempju):
any major surgery, defined as surgery that requires general or spinal anesthesia, performed within the 12-hour period immediately preceding drug infusion, or any postoperative patient who demonstrates evidence of active bleeding, or any patient with planned or anticipated surgery during the drug infusion period.
kull kirurġija maġġura, definita bħala kirurġija li jeħtiġilha anestesija ġenerali jew fis - sinsla, li tkun saret sa 12- il siegħa qabel ma ssir l- infużjoni tal- mediċina, jew kull pazjent li tkun saritlu operazzjoni u li jkollu fsada attiva, jew kull pazjent li jkun se jagħmel operazzjoni pjanata jew antiċipata matul iż- żmien ta ’ l- infużjoni;
history of severe head trauma that required hospitalization, intracranial or intraspinal surgery, or haemorrhagic stroke within the previous 3 months, or any history of intracerebral arteriovenous malformation, cerebral aneurysm, or central nervous system mass lesion; patients with an epidural catheter or who are anticipated to receive an epidural catheter during drug infusion
passat mediku ta ’ xi trawma gravi fir- ras li tkun ħtieġet żmien fi sptar, kirurġija intrakranika jew intraspinali, jew attakk pupletku b’ emorraġija sa 3 xhur qabel, jew kull storja ta ’ xi malformazzjoni arterjovenali intraċerebrali, anewriżma ċerebrali, jew xi leżjoni serja tas- sistema nervuża ċentrali; pazjenti b’ kateter epidurali jew li jkun se jingħatalhom kateter epidurali matul l- infużjoni tal- mediċina;
history of congenital bleeding diatheses gastrointestinal bleeding within the last 6 weeks that has required medical intervention unless definitive surgery has been performed
passat mediku ta ’ dijateżi konġenitali ta ’ fsada fsada gastrointestinali matul is- 6 ġimgħat ta ’ qabel, li kienet teħtieġ intervent mediku, sakemm ma tkunx saret kirurġija definittiva
trauma patients at increased risk of bleeding
pazjenti bi trawma li jkollhom riskju akbar ta ’ fsada
Patients with single organ dysfunction and recent surgery Xigris is not approved for the treatment of patients with single organ dysfunction and should not be used in this particular subgroup of patients, especially if they had recent surgery (within 30 days).
Pazjenti b’ disfunzjoni ta ’ organu wieħed u kirurġija recenti
In each of two randomised, placebo-controlled trials, PROWESS and ADDRESS (see section 5.1), 28- day and in-hospital mortality were higher in patients treated with drotrecogin alfa (activated) compared to placebo for the sub-population of patients with single organ dysfunction and recent surgery (n=98 in PROWESS and n=636 in ADDRESS).
Xigris mhuwiex approvat għal kura ta ’ pazjenti b’ disfunzjoni ta ’ organu wieħed u m’ għandux jintuża f’ dan is- sottogrupp partikolari ta ’ pazjenti, speċjalment jekk kellhom xi kirurġija reċenti (f’ dawn l - aħħar 30 ġurnata). F’ kull wieħed minn żewġ studji kkontrollati bi plaċebo u magħmula b’ mod arbitrarju, PROWESS u ADDRESS (ara sezzjoni 5. 1), il- mortalità wara t- 28 ġurnata u f’ pazjenti fl - isptar kienu ogħla fil- pazjenti li ġew mogħtija d- drotrecogin alfa (attivat) meta kkomparat mal- plaċebo fis- sottopopolazzjoni ta ’ pazjenti b’ disfunzjoni ta ’ organu wieħed u kirurġija reċenti (n=98 f’ PROWESS u n=636 f’ ADDRESS)
Bleeding Drotrecogin alfa (activated) increases the risk of bleeding.
Fsada Drotrecogin alfa (attivat) iżid ir- riskju ta ’ fsada.
In the following conditions, the risks of the administration of Xigris should be weighed against the anticipated benefits:
Fil- kundizzjonijiet li ġejjin, ir- riskji ta ’ l- għoti ta ’ Xigris għandhom jitqiesu flimkien mal- benefiċċji mistennija:
• Recent administration (within 3 days) of thrombolytic therapy • Recent administration (within 7 days) of oral anticoagulants • Recent administration (within 7 days) of aspirin or other platelet inhibitors • Recent (within 3 months) ischaemic stroke • Any other condition in which the physician considers significant bleeding is likely
L- għoti reċenti (sa 3 ijiem) ta ’ terapija trombolitika L- għoti reċenti (sa 7 ijiem) ta ’ antikoagulanti orali L- għoti reċenti (sa 7 ijiem) ta ’ aspirini jew inibituri oħrajn tal- plejtlets Puplesija iskemika reċenti (sa 3 xhur) Kull kundizzjoni oħra meta t- tabib iqis li jkun hemm il- possibilità ta ’ fsada sinifikanti
For procedures with an inherent bleeding risk, discontinue Xigris for 2 hours prior to the start of the procedure.
3 Għal proċeduri b’ riskju inerenti ta ’ fsada, waqqaf Xigris sagħtejn qabel tibda l- proċedura.
The incidence of serious bleeding events with Xigris was higher in
Xigris jista ’ jinbeda 12- il siegħa wara l- kirurġija jew proċeduri invażivi maġġuri jekk tkun intlaħqet emostażi xierqa.
3 patients with recent [within 30 days] surgery than in “ medical” patients without surgery (see section 4.8).
L- inċidenza ta ’ każijiet serji ta ’ fsada b’ Xigris kienu ogħla f’ pazjenti li kellhom kirurġija reċenti [fi żmien 30 ġurnata] milli f’ pazjenti ‘ tal- mediċina ’ li ma kellhom ebda kirurġija (ara sezzjoni 4. 8).
Xigris may be restarted immediately after uncomplicated less invasive procedures if adequate haemostasis has been achieved.
Dan ir- riskju ta ’ fsada jrid jiġi meqjus meta jiġi kkunsidrat ir- riskju u l- benefiċċju għal pazjenti individwali. Xigris jista ’ jerġa ’ jinbeda minnufih wara proċeduri inqas invażivi u mhux ikkomplikati jekk tkun intlaħqet emostażi xierqa.
As a component of routine care, measures of haemostasis (e. g., activated partial thromboplastin time (APTT), prothrombin time (PT) and platelet count) should be obtained during the infusion of Xigris.
Bħala parti mill- assistenza ta ’ rutina, għandhom jittieħdu miżuri ta ’ l- emostażi (eż., il- ħin parzjali ta ’ thromboplastin attivat (APTT), il- ħin ta ’ prothrombin (PT) u l- għadd tal- plejtlets) waqt l- infużjoni ta ’ Xigris.
If sequential tests of haemostasis indicate an uncontrolled or worsening coagulopathy that significantly increases the risk of bleeding, the benefits of continuing the infusion must be weighed against the potential increased risk of bleeding for that patient.
Jekk it- testijiet sekwenzjali ta ’ l- emostażi juru koagulopatija li ma tkunx kontrollata jew li tkun sejra għall- agħar tant li jikber ir- riskju ta ’ fsada, wieħed għandu jqis il- benefiċċji li titkompla l - infużjoni, flimkien mar- riskju potenzjali akbar ta ’ fsada għall- pazjent.
Laboratory tests Drotrecogin alfa (activated) has minimal effect on the PT.
Testijiet tal- laboratorju Drotrecogin alfa (attivat) għandu effett minimu fuq il- PT.
Prolongation of the APTT in patients with severe sepsis receiving Xigris may be due to the underlying coagulopathy, the pharmacodynamic effect of drotrecogin alfa (activated), and/ or the effect of other concurrent medicinal products.
It- titwil ta ’ l- APTT f’ pazjenti b’ sepsis gravi li jkunu qegħdin jieħdu Xigris jista ’ jkun ġej minn koagulopatija eżistenti, mill- effett farmakodinamiku ta ’ drotrecogin alfa (attivat), u/ jew mill- effett ta ’ prodotti mediċinali oħra li jkunu qegħdin jittieħdu fl- istess ħin.
The pharmacodynamic effect of drotrecogin alfa (activated) on the APTT assay is dependent on the reagent and instrument used to perform the assay and the time that elapses between sample acquisition and assay performance.
L- effett farmakodinamiku ta ’ drotrecogin alfa (attivat) fuq l- analiżi ta ’ l - APTT jiddependi mir- reaġent u mill- istrument użati għall- analiżi u mill- ħin li jgħaddi bejn it- teħid tal - kampjun u meta ssir l- analiżi.
Drotrecogin alfa (activated) that is present in a blood or plasma sample drawn from a patient who is being infused with the drug will be gradually neutralized by endogenous plasma protease inhibitors present in the sample.
Drotrecogin alfa (attivat) li jkun preżenti f’ kampjun tad- demm jew tal - plażma meħud minn pazjent li jkun qiegħed jieħu infużjoni tal- mediċina jiġi newtralizzat bil- mod il - mod permezz ta ’ inibituri endoġeni tal- proteażi tal- plażma li jkunu preżenti fil- kampjun.
Virtually no measurable activity of drotrecogin alfa (activated) is present 2 hours after obtaining the blood sample.
Tista ’ tgħid li l- ebda attività ta ’ drotrecogin alfa (attivat) li tista ’ titkejjel ma tkun preżenti sagħtejn wara li jkun ittieħed il- kampjun tad- demm.
Due to these biological and analytical variables, the APTT should not be used to assess the pharmacodynamic effect of drotrecogin alfa (activated).
Minħabba dawn il- fatturi bijoloġiċi u analitiċi varji, l- APTT m’ għandux jintuża biex jitkejjel l- effett farmakodinamiku ta ’ drotrecogin alfa (attivat).
In addition, approximately 2 hours after terminating the infusion of the drug, there is virtually no measurable activity of drotrecogin alfa (activated) remaining in the circulation of the patient; blood samples drawn for APTT determination after this point are no longer affected by the drug.
Barra minn hekk, xi sagħtejn wara li tintemm l- infużjoni tal- mediċina, ma jkun għad fadal kważi l- ebda ta ’ drotrecogin alfa (attivat) li tista ’ titkejjel fiċ- ċirkolazzjoni tal- pazjent; il- kampjuni tad- demm miġbura biex ikun determinat l- APTT minn issa ’ l quddiem ma jibqgħux effettwati mill- mediċina.
The interpretation of sequential determinations of the PT and/ or APTT should take these variables into consideration.
Wieħed għandu jżomm f’ moħħu dawn il- fatturi varjabbli meta jiġi biex jinterpreta t- testijiet sekwenzjali tal- PT u/ jew ta ’ l- APTT.
Drotrecogin alfa (activated) present in plasma samples does not interfere with one-stage factor assays based on the PT (such as Factors II, V, VII and X assays).
Minħabba li drotrecogin alfa (attivat) jista ’ jeffettwa l- analiżi ta ’ l- APTT, drotrecogin alfa (attivat) li jkun preżenti fil- kampjuni tal- plażma jista ’ jfixkel l- analiżi tal- koagulazzjoni magħmula f’ daqqa, ibbażata fuq l- APTT (bħall- analiżi għall- fattur VIII, IX u XI).
If sequential measures of coagulopathy (including platelet count) indicate severe or worsening coagulopathy, the risk of continuing the infusion should be weighed against the expected benefit.
Jekk il- miżuri sekwenzjali tal- koagulopatija (fosthom l- għadd tal- plejtlets) juru koagulopatija gravi jew sejra għall- agħar, wieħed għandu jqis bejn ir- riskju li titkompla l- infużjoni u l- benefiċċju mistenni.
Immunogenicity In adult patients in severe sepsis clinical studies, the frequency of anti-human Activated Protein C IgA/ IgG/ IgM antibodies or neutralizing antibodies is low and is similar between drotrecogin alfa (activated) and placebo-treated patients tested.
L- Immunoġeniċità F’ studji kliniċi ta ’ pazjenti adulti b’ sepsis gravi, il- frekwenza ta ’ antikorpi IgA/ IgG/ IgM kontra l - Proteina Ċ Attivata umana jew ta ’ antikorpi ta ’ newtralizzazzjoni hija baxxa u fil- pazjenti taħt studju, hija l- istess kemm għal dawk ikkurati b’ drotrecogin alfa (attivat) u kemm għal dawk ikkurati bi plaċebo.
In patients developing antibodies adverse events were not more frequent in drotrecogin alfa (activated) than in placebo patients.
F’ pazjenti li jkollhom l- antikorpi, l- avvenimenti avversi f’ dawk ikkurati b’ drotrecogin alfa (attivat) ma kienux iżjed frekwenti minn dawk ikkurati bi plaċebo.
There was no evidence that the antibodies detected represented a specific immune response to drotrecogin alfa (activated) therapy.
Ma kien hemm ebda evidenza li l - antikorpi li nstabu jirrappreżentaw xi rispons immuni speċifiku għat- terapija b’ drotrecogin alfa (attivat).
There have been no clinical trials in severe sepsis specifically studying drotrecogin alfa (activated) re- administration.
F’ sepsis gravi, m’ hemmx studji kliniċi li b’ mod speċifiku investigaw l- għoti mill- ġdid ta ’ drotrecogin alfa (attivat).
However, a small number of patients in severe sepsis controlled clinical trials received a prior course of drotrecogin alfa (activated).
Madankollu, f’ studji kliniċi kkontrollati, numru żgħir ta ’ pazjenti b’ sepsis gravi kienu rċevew kors qabel ta ’ drotecogin alfa (attivat).
No hypersensitivity reactions were reported in these patients.
F’ dawn il- pazjenti ma ġewx irrapportati reazzjonijiet ta ’ sensittività eċċessiva.
Samples available were subsequently tested and all were negative for anti-human Activated Protein C antibody.
Sussegwentement ġew eżaminati xi kampjuni u kollha kienu negattivi għall- antikorp kontra l- Proteina Ċ Attivata umana.
No anti-activated Protein C antibody formation was detected in healthy subjects, even after repeat administration.
Ma nstabux formazzjonijiet ta ’ antikorpi kontra l- Proteina Ċ attivata f’ individwi b’ saħħithom, ukoll jekk ħadu l- kura aktar minn darba.
However, the possibility of allergic reactions to constituents of the preparation cannot be completely excluded in certain predisposed patients.
Madankollu, il- possibilità ta ’ reazzjoni allerġika għal xi kostitwenti tas- sustanza ma tistax titneħħa għal kollox f’ xi pazjenti li jkunu predisposti.
If allergic or anaphylactic reactions occur, treatment should be discontinued immediately and appropriate therapy initiated.
Jekk iseħħu reazzjonijiet allerġiċi jew anafilattiċi, il- kura għandha titwaqqaf minnufih u minflokha tibda terapija xierqa.
If Xigris is readministered to patients, caution should be employed.
Jekk Xigris jerġa ’ jingħata lill- pazjenti, wieħed għandu joqgħod attent.
4 cardiovascular organ dysfunction.
4 Pazjenti f’ età pedjatrika
This trial was stopped for futility after 477 patients had received the study drug (out of 600 patients intended).
Dawn it- testijiet twaqqfu minħabba l- inutilità wara li 477 kienu rċevew l- mediċina studjata (minn 600 li suppost kellhom jeħduha).
A planned interim analysis (with 400 patients enrolled) showed a low likelihood of demonstrating a significant difference in the primary endpoint of “ Composite Time to Complete Organ Failure Resolution” (CTCOFR score of 9.8 versus 9.7 mean days over 14 days).
Analiżi parzjali li kienet ippjanata (fuq 400 pazjent irreġistrat) uriet li ftit kien hemm iċ- ċans li toħroġ xi differenza sinifikanti fil- konklużjoni ewlenija tar - “ Riżoluzzjoni Ħin Kompożitu sa meta l- Organu Jieqaf Jaħdem Għal Kollox ” (Skor CTCOFR ta ’ 9. 8 kontra 9. 7 medja ta ’ ġranet iktar minn 14- il ġurnata).
There was also no difference in 28-day mortality (17.1% versus 17.3% in the Xigris and placebo groups, respectively).
Lanqas ma kien hemm differenza fil- mortalità fuq 28 ġurnata (17. 1% kontra 17. 3% fil - gruppi Xigris u plaċebo, rispettivament).
Investigators attributed 2 deaths in the Xigris group and 5 deaths in the placebo group to bleeding events.
L- investigaturi attribwew 2 imwiet fil- grupp Xigris u 5 imwiet fil- grupp plaċebo għal każi ta ’ fsada.
There was a higher rate of central nervous system (CNS) bleeding in the drotrecogin alfa (activated) versus the placebo group.
Fil- grupp drotrecogin alfa (attivata) kien hemm rata ogħla ta ’ fsada fis- sistema nervuża ċentrali (CNS) milli fil- grupp plaċebo.
Over the infusion period (study days 0-6) the number of patients experiencing CNS bleeding was 5 versus 1 (2.1% versus 0.4%) for the overall population (drotrecogin alfa (activated) versus placebo), with 4 of the 5 events in the drotrecogin alfa (activated) group occurring in patients ≤ 60 days old or ≤ 3.5 kg bodyweight.
Waqt il- perjodu ta ’ l- infużjoni (ġranet ta ’ studju 0- 6) l- għadd ta ’ pazjenti li kellhom fsada fis- CNS kien ta ’ 5 kontra 1 (2. 1% kontra 0. 4%) għall- popolazzjoni totali (drotrecogin alfa (attivat) kontra plaċebo), b’ 4 mill- 5 każi fil- grupp drotrecogin alfa (attivat) ikunu ta ’ pazjenti ta ’ ≤ 60 ġurnata jew b’ piż ≤ minn 3. 5kg.
Fatal CNS bleeding events, serious bleeding events (over the infusion period and over the 28-day study period), serious adverse events, and major amputations were similar in the drotrecogin alfa (activated) and placebo groups.
L- għadd ta ’ każi ta ’ fsada fatali fis- CNS, każi ta ’ fsada gravi (waqt il- perjodu ta ’ infużjoni u waqt iż- żmien ta ’ studju ta ’ 28 ġurnata), każi gravi avversi, u każi ta ’ amputazzjonijiet maġġuri kien l- istess fil- grupp drotrecogin alfa (attivat) u fil- grupp plaċebo.
To be taken into consideration by patients on a controlled sodium diet.
Dan il- prodott mediċinali fih madwar 68 mg ta ’ sodium. Pazjenti li qegħdin fuq dieta ta ’ restrizzjoni ta ’ sodium għandhom jagħtu kas ta ’ dan il- fatt.
Caution should be employed when Xigris is used with other drugs that affect haemostasis (see sections 4.3 and 4.4) including Protein C, thrombolytics (e. g. streptokinase, tPA, rPA and urokinase), oral anticoagulants (e. g. warfarin), hirudins, antithrombin, aspirin and other anti platelets agents, e. g. non- steroidal anti-inflammatory drugs, ticlopidine and clopidogrel, glycoprotein IIb/ IIIa antagonists (such as abciximab, eptifibatide, tirofiban) and prostacyclins such as iloprost.
Wieħed għandu joqgħod attent meta Xigris jintuża ma ’ mediċini oħra li jeffettwaw l- emostażi (ara sezzjonijiet 4. 3 u 4. 4) fosthom il- Proteina Ċ, trombolitiċi (eż. streptokinase, tPA, rPA u urokinase), antikoagulanti orali (eż. warfarin), hirudins, antithrombin, aspirina u sustanzi oħra li għandhom effett kontra l- plejtlets, eż. mediċini kontra l- infjammazzjoni li mhumiex sterojdi, ticlopidine, u clopidogrel, antagonisti tal- glikoproteini IIb/ IIIa (bħal abciximab, eptifibatide, tirofiban) u prostaċiklini bħal iloprost.
Co-administration of low-dose heparin for prophylaxis of venous thrombotic events (VTE) Low-dose heparin for VTE prophylaxis may be co-administered with drotrecogin alfa (activated).
Teħid flimkien ma ’ doża baxxa ta ’ eparina mgħotija sabiex tilqa ’ kontra każijiet ta ’ trombożi fil- vini (VTE) Doża baxxa ta ’ eparina mgħotija sabiex tilqa ’ kontra VTE tista ’ tingħata flimkien ma ’ drotrecogin alfa (attivat).
In a randomised study of heparin versus placebo (XPRESS) in 1935 adult severe sepsis patients, all treated with drotrecogin alfa (activated), prophylactic heparin did not adversely affect mortality (heparin 28.3% versus placebo 31.9% in the overall ITT population, and heparin 30.3% versus placebo 26.9% in patients with multiple organ dysfunction treated within 24 hours of their first sepsis-induced organ dysfunction (n=890)).
Fi studju kliniku ta ’ eparina kontra plaċebo (XPRESS) magħmul b’ mod arbitrarju fuq 1935 pazjent adult b’ sepsis gravi, kollha kkurati b’ drotrecogin alfa (attivat), eparina mgħotija bħala profilassi m’ affettwatx b’ mod negattiv il- mortalità (eparina 28. 3% kontra plaċebo 31. 9% fil - popolazzjoni ITT kollha u eparina 30. 3% kontra plaċebo 26. 9% f’ pazjenti b’ disfunzjoni ta ’ organi multipli kkurati fi żmien 24 siegħa mill- ewwel disfunzjoni ta ’ organu tagħhom ikkawżat mis- sepsis (n=890).
In the subgroup of 885 patients who were already receiving prophylactic heparin at study entry, mortality was 26.9% in the group randomised to continue heparin versus 35.6% in the group whose randomisation (to placebo) led to the discontinuation of heparin.
Fis- sottogrupp ta ’ 885 pazjent li meta beda l- istudju kliniku kienu diġa ’ qegħdin jirċievu eparina bħala profilassi, il- mortalità kienet ta ’ 26. 9% fil- grupp li b’ mod arbitrarju baqgħu jirċievu l - eparina kontra dik ta ’ 35. 6% fil- grupp li minħabba l- arbitrarjetà (li jirċievu plaċebo) waslithom biex ma jibqgħux jirċievu l- eparina.
However the reasons for this difference are unknown and could be related to other factors.
Madankollu, m’ humiex magħrufa r- raġunijiet ta ’ din id- differenza u jistgħu jkunu marbuta ma ’ fatturi oħra.
Additionally there was no increased risk of serious bleeding, including central nervous system (CNS) bleeding.
Barra minn hekk ma kien hemm ebda żieda fir- riskju ta ’ fsada serja, li tinkludi fsada fis- sistema nervuża ċentrali (CNS).
Prophylactic heparin increased the risk of non-serious bleeding (see section 4.8).
Eparina mgħotija bħala profilassi żdiedet ir- riskju ta ’ dik il- fsada li m’ hijiex serja (ara sezzjoni 4. 8).
There was no statistical difference in the rates of VTE between study arms.
Statistikament, ma kien hemm ebda differenza fir- rati ta ’ VTE bejn iż- żewġ fergħat ta ’ studju.
4.6 Pregnancy and lactation
5 4. 6 Tqala u Treddigħ
Animal studies with respect to effects on pregnancy, embryonal/ foetal development, parturition and postnatal development have not been conducted with Xigris.
Ma sarux studji fuq l- annimali dwar l- effetti ta ’ Xigris fuq it- tqala, fuq l- iżvilupp ta ’ l- embriju/ fetu, fuq it- twelid u fuq l- iżvilupp wara t- twelid.
Therefore, the potential risk for humans is unknown.
Għalhekk ir- riskju potenzjali għall- bnedmin mhuwiex magħruf.
Xigris should not be used during pregnancy unless clearly necessary.
Xigris m’ għandux jintuża waqt it- tqala sakemm ma jkunx meħtieġ b’ mod ċar.
It is not known whether Xigris is excreted in human milk or if there is a potential effect on the breast- fed infant.
Mhux magħruf jekk Xigris joħroġx fil- ħalib tal- bniedem jew jekk hemm xi effett potenzjali fuq it - tarbija li titradda ’.
Therefore, the patient should not breast feed whilst treated with Xigris.
Għalhekk il- pazjenta m’ għandhiex tradda ’ waqt li tkun qiegħda tieħu Xigris.
Xigris increases the risk of bleeding.
Xigris iżid ir- riskju ta ’ fsada.
5 The Phase 3 international, multi-centre, randomised, double-blind, placebo-controlled clinical trial (PROWESS) involved 850 drotrecogin alfa (activated)-treated and 840 placebo-treated patients.
Fl- istudju kliniku Fażi 3 internazzjonali, multiċentriku, magħmul b’ mod arbitrarju, double- blind, ikkontrollat bi plaċebo (PROWESS) ħadu sehem 850 pazjent li ħadu drotrecogin alfa (attivat) u 840 li ħadu l- plaċebo.
The percentage of patients experiencing at least one bleeding event in the two treatment groups was 24.9% and 17.7%, respectively.
Il- perċentwal ta ’ pazjenti li għaddew minn għallinqas każ wieħed ta ’ fsada fiż- żewġ gruppi kien ta ’ 24. 9% u 17. 7% rispettivament.
In both treatment groups, the majority of bleeding events were ecchymosis or gastrointestinal tract bleeding.
Fiż- żewġ gruppi, il- biċċa l- kbira tal- każijiet ta ’ fsada kienu ta ’ ekkimożi jew ta ’ fsada gastrointestinali.
The difference in the incidence of serious bleeding events between the two treatment groups occurred primarily during study drug administration.
Id- differenza fl- inċidenza ta ’ każijiet serji ta ’ fsada bejn iż- żewġ gruppi seħħet prinċipalment waqt l- għoti tal- mediċina fl- istudju.
A total of 2378 adult patients with severe sepsis received drotrecogin alfa (activated) in a Phase 3b, international, single-arm, open-label clinical trial (ENHANCE).
Għadd ta ’ 2, 378 pazjent adult b’ sepsis gravi ħadu drotrecogin alfa (attivat) fl- istudju kliniku Fażi 3b, internazzjonali, f’ fergħa waħda, fil- miftuħ (ENHANCE).
The incidence of serious bleeding events in the PROWESS and ENHANCE studies is provided below.
L- inċidenza ta ’ każijiet serji ta ’ fsada fl- istudji PROWESS u ENHANCE qiegħda tidher aktar ’ l isfel.
In these studies serious bleeding events included any intracranial haemorrhage, any life-threatening or fatal bleed, any bleeding event requiring the administration of ≥ 3 units of packed red blood cells per day for 2 consecutive days, or any bleeding event assessed as serious by the investigator.
F’ dawn l- istudji, il- każijiet ta ’ fsada serja kienu jiġbru kull emorraġija intrakranika, kull fsada li kienet ta ’ periklu għall- ħajja, kull każ ta ’ fsada li kienet teħtieġ l- għoti ta ’ ≥ 3 unitajiet kuljum ta ’ ċelloli ħomor tad- demm ippakkjati għal jumejn wara xulxin, jew kull każ ta ’ fsada meqjus bħala serju mill - investigatur.
A Phase 3b international, multi-centre, randomised, double-blind, placebo-controlled clinical trial (ADDRESS) of adult severe sepsis patients at low risk of death, involved 1317 drotrecogin alfa (activated)-treated and 1293 placebo-treated patients.
Fl- istudju kliniku Fażi 3b, internazzjonali, multiċentriku, magħmul b’ mod arbitrarju, double- blind u kkontrollat bi plaċebo (ADDRESS) ta ’ pazjenti adulti b’ sepsis gravi b’ riskju żgħir ta ’ mewt, ħadu sehem 1, 317- il pazjent li ħadu drotrecogin alfa (attivat) u 1, 293 li ħadu l- plaċebo.
The percentage of patients experiencing at least one bleeding event in the two treatment groups was 10.9% and 6.4%, respectively (p < 0.001).
Il- perċentwal ta ’ pazjenti li għaddew minn għallinqas każ wieħed ta ’ fsada fiż- żewġ gruppi kien ta ’ 10. 9% u 6. 4% rispettivament (p < 0. 001).
Bleeding events included serious bleeding events, bleeding events assessed as possibly study-drug related by the investigator, bleeding events associated with the need for a red blood cell transfusion, and bleeding events that led to permanent discontinuation of the study drug.
Fost il- każijiet ta ’ fsada kien hemm dawk serji, dawk li l- investigatur ikkunsidra bħala li kellhom x’ jaqsmu mal- mediċina li ngħatat waqt l- istudju, dawk li kellhom x’ jaqsmu mal- ħtieġa ta ’ trasfużjoni ta ’ ċelloli ħomor tad- demm, u dawk li wasslu biex titwaqqaf għal kollox il- mediċina li kienet qed tiġi studjata.
In the ADDRESS trial, serious bleeding events included any fatal bleed, any life-threatening bleed, any CNS bleed, or any bleeding event assessed as serious by the investigator.
Fl- istudju ADDRESS, il- każijiet ta ’ fsada serja kienu jinkludu dawk li jwasslu għall- mewt, dawk li jipperikolaw il- ħajja, dawk fis- sistema nervuża ċentrali (CNS), jew dawk meqjusa bħala serji mill- investigatur.
Serious bleeding events during the infusion period The following table lists the percent of patients in PROWESS and ENHANCE experiencing serious bleeding events by site of haemorrhage during the study drug infusion period (defined as the duration of infusion plus the next full calendar day following the end of the infusion).
Fit- tabella ta ’ taħt jinstab il- perċentwal ta ’ pazjenti fi PROWESS u ENHANCE li kellhom każijiet serji ta ’ fsada skond il- post ta ’ l- emorraġija matul il- perijodu ta ’ l- infużjoni tal- mediċina studjata (definit bħala l- perjodu ta ’ l- infużjoni magħduda miegħu l- ġurnata kalendarja sħiħa li jmiss wara t - tmiem ta ’ l- infużjoni).
Drotrecogin alfa (activated)
Drotrecogin alfa (attivat)
Site of haemorrhage Gastrointestinal Intra-abdominal Intra-thoracic Retroperitoneal Central Nervous
Post ta ’ l- emorraġija Gastrointestinali Intra- abdominali Intra- toraċiku Retroperitoneali Sistema Nervuża Ċentrali (CNS) 1
[PROWESS] N=850 5 (0.6%) 2 (0.2%) 4 (0.5%) 3 (0.4%)
[PROWESS] N=850 5 (0. 6%) 2 (0. 2%) 4 (0. 5%) 3 (0. 4%) 2 (0. 2%)
[PROWESS] N=840 4(0.5%) 3 (0.4%) 0 0
[PROWESS] N=840 4 (0. 5%) 3 (0. 4%) 0 0 0
[ENHANCE] N=2378 19 (0.8%) 18 (0.8%) 11 (0.5%) 4 (0.2%)
[ENHANCE] N=2378 19 (0. 8%) 18 (0. 8%) 11 (0. 5%) 4 (0. 2%) 15 (0. 6%)
System (CNS)1
Ġenitourinarju Ġilda/ tessut artab Nażofarinġali Ġog/ Għadma Post mhux magħruf2
2 (0.2%)
2 (0. 2%) 1 (0. 1%) 0 0 1 (0. 1%)
15 (0.6%)
0 0 0 0 1 (0. 1%)
1
0 16 (0. 7%) 4 (0. 2%) 1 (0. 04%) 6 (0. 3%) 853 (3. 6%)
Genitourinary Skin/ soft tissue Nasopharyngeal Joint/ Bone Site unknown2 Total
Total
2 (0.2%) 1 (0.1%) 0 0 1 (0.1%) 20 (2.4%)
20 (2. 4%)
0 0 0 0 1 (0.1%) 8 (1.0%)
8 (1. 0%)
Petechial, parenchymal, subarachnoid, subdural, and stroke with haemorrhagic transformation.
1 Fsada fis- CNS hija definita bħala kull fsada fis- sistema ċentrali nervuża, fosthom dawn it- tipi ta ’ emorraġija: petekjali, parenkimali, subaraknojdi, subdurali u attakk pupletku bi trasformazzjoni f’ emorraġija.
2 Patients requiring the administration of ≥ 3 units of packed red blood cells per day for 2 consecutive days without an identified site of bleeding 3 In ENHANCE six patients experienced multiple serious bleeding events during the study drug infusion period (94 events observed in 85 patients).
2 Pazjenti li jkunu jeħtieġu ≥ 3 unitajiet kuljum ta ’ ċelluli ħomor tad- demm ikkonċentrati għal jumejn wara xulxin bla ma jkun idetifikat il- post tal- fsada 3 F’ ENHANCE sitt pazjenti kellhom diversi każijiet ta ’ fsada serja matul il- perijodu ta ’ l- infużjoni tal- mediċina studjata (kienu osservati 94 każ f’ 85 pazjent).
6 During the infusion period in PROWESS and ENHANCE the incidence of serious bleeding events with Xigris was numerically higher in patients with recent [within 30 days] surgery than in patients without surgery (PROWESS:
Waqt il- perijodu ta ’ infużjoni fi PROWESS u ENHANCE, l- inċidenza ta ’ każijiet serji ta ’ fsada bi Xigris kienet numerikament ogħla f’ pazjenti li kellhom kirurġija reċenti [fi żmien 30 ġurnata] milli f’ pazjenti li ma kellhom ebda kirurġija (PROWESS:
3.3% vs 2.0%; ENHANCE:
3. 3% kontra 2. 0%, ENHANCE:
5.0% vs 3.1% respectively.
5. 0% kontra 3. 1% rispettivament.
Placebo rates in PROWESS 0.4% vs 1.2% respectively).
Ir- rati ta ’ plaċebo fi PROWESS 0. 4% kontra 1. 2% rispettivament)
In ADDRESS, the percent of treated patients experiencing a serious bleeding event by site of haemorrhage was similar to that observed in PROWESS.
F’ ADDRESS, il- perċentwal ta ’ pazjenti kkurati li kellhom każ serju ta ’ fsada skond il- post ta ’ l - emorraġija kien l- istess bħal dak osservat fi PROWESS.
The incidence of serious bleeding events during infusion (defined as study Day 0 through study Day 6) was 31 (2.4%) and 15 (1.2%) in drotrecogin alfa (activated)-treated and placebo-treated patients, respectively (p=0.02).
L- inċidenza ta ’ każijiet ta ’ fsada serja waqt l - infużjoni (definita bħala Ġurnata ta ’ Studju 0 sa Ġurnata ta ’ Studju 6) kienet ta ’ 31 (2. 4%) u ta ’ 15 (1. 2%) fil- pazjenti li ħadu drotrecogin alfa (attivat) u l- plaċebo, rispettivament (p=0. 02).
The incidence of CNS bleeds during infusion was 4 (0.3%) and 3 (0.2%) for drotrecogin alfa (activated)-treated and placebo-treated patients, respectively.
L- inċidenza ta ’ fsada fis- Sistema Nervuża Ċentrali waqt l- infużjoni kienet ta ’ 4 (0. 3%) u ta ’ 3 (0. 2%) għal dawk li ħadu drotrecogin alfa (attivat) u dawk li ħadu l- plaċebo, rispettivament.
Recent surgery (within 30 days prior to study entry) was associated with a numerically higher risk of serious bleeding during infusion in both the Xigris-treated and the placebo-treated patients (Xigris:
Kirurġija reċenti (sa 30 ġurnata qabel beda l- istudju) kienet assoċjata ma ’ għadd ogħla ta ’ riskju ta ’ fsada serja waqt l - infużjoni, kemm fil- pazjenti li ħadu Xigris kif ukoll f’ dawk li ħadu l- plaċebo (Xigris:
3.6% in patients with recent surgery versus 1.6% in patients without recent surgery; placebo:
3. 6% fil- pazjenti li kellhom kirurġija reċenti kontra 1. 6% fil- pazjenti li ma kellhomx kirurġija reċenti; plaċebo:
1.6% versus 0.9% respectively).
1. 6% kontra 0. 9% rispettivament).
In XPRESS, a randomised study of prophylactic heparin versus placebo in adult severe sepsis patients, all treated with drotrecogin alfa (activated), serious bleeding rates were consistent with those observed in previous studies over the treatment period of 0-6 days, and prophylactic heparin did not increase the risk of serious bleeding compared to placebo (2.3% vs 2.5%, respectively), including CNS bleeding (0.3% on both arms).
F’ XPRESS, studju kliniku magħmul b’ mod arbitrarju ta ’ eparina mgħotija bħala profilassi kontra plaċebo f’ pazjenti adulti b’ sepsis gravi, kollha kkurati b’ drotrecogin alfa (attivat), ir- rati ta ’ fsada serja matul il- perijodu ta ’ kura ta ’ 0- 6 ġranet, kienu konsistenti ma ’ dawk ta ’ studji kliniċi preċedenti, u eparina mgħotija bħala profilassi ma żiedetx ir- riskju ta ’ fsada serja meta mqabbla ma ’ plaċebo (2. 3% kontra 2. 5%, rispettivament), inkluż il- fsada fis- CNS (0. 3% fiż- żewġ fergħat).
However prophylactic heparin increased the risk of non-serious bleeding compared with placebo (8.7% vs 5.7%, respectively; p= 0.0116).
Madankollu eparina mgħotija bħala profilassi żiedet ir- riskju ta ’ dik il- fsada li m’ hijiex serja meta mqabbla ma ’ plaċebo (8. 7% kontra 5. 7%, rispettivament; p=0. 0116)
Serious bleeding events during the 28-day study period In PROWESS, the incidence of serious bleeding events during the 28-day study period was 3.5% and 2.0% in drotrecogin alfa (activated)-treated and placebo-treated patients, respectively.
Każijiet serji ta ’ fsada matul il- perijodu ta ’ studju ta ’ 28 ġurnata Fi PROWESS, l- inċidenza ta ’ każijiet serji ta ’ fsada matul il- perijodu ta ’ studju ta ’ 28 ġurnata kien ta ’ 3. 5% u ta ’ 2. 0% fil- pazjenti li ħadu drotrecogin alfa (attivat) u dawk li ħadu l- plaċebo, rispettivament.
The incidence of CNS bleeds during the 28-day study period was 0.2% and 0.1% for drotrecogin alfa (activated)- treated and placebo-treated patients, respectively.
L- inċidenza ta ’ każijiet ta ’ fsada fis- Sistema Nervuża Ċentrali matul it- terminu ta ’ studju ta ’ 28 ġurnata kienet ta ’ 0. 2% u ta ’ 0. 1% fil- pazjenti li ħadu drotrecogin alfa (attivat) u l- plaċebo, rispettivament.
The risk of CNS bleeding may increase with severe coagulopathy and severe thrombocytopenia (see sections 4.3 and 4.4).
Ir- risk ta ’ fsada fis- ĊNS jista ’ jiżdied jekk ikun hemm koagulopatija gravi u tromboċitopenija gravi (ara Sezzjonijiet 4. 3 u 4. 4).
In the open-label ENHANCE study, the incidence of serious bleeding events during the 28-day study period was 6.5%, and the incidence of CNS bleeds during the 28-day study period was 1.5%.
7 Fl- istudju bil- miftuħ ENHANCE, l- inċidenza ta ’ każijiet serji ta ’ fsada matul il- perijodu ta ’ studju ta ’ 28 ġurnata kienet ta ’ 6. 5%, u l- inċidenza ta ’ fsada fis- CNS fl- istess perijodu ta ’ żmien kienet ta ’ 1. 5%.
In the placebo-controlled ADDRESS study, the incidence of serious bleeding events during the 28-day study period was 51 (3.9%) and 28 (2.2%) in drotrecogin alfa (activated)-treated and placebo-treated patients, respectively (p=0.01).
Fl- istudju ADDRESS ikkontrollat mill- plaċebo, l- inċidenza ta ’ każijiet serji ta ’ fsada matul il- perijodu ta ’ studju ta ’ 28 ġurnata kienet ta ’ 51 (3. 9%) u ta ’ 28 (2. 2%) fil- pazjenti li ħadu drotrecogin alfa (attivat) u l- plaċebo, rispettivament (p=0. 01).
The incidence of CNS bleeds during the 28-day study period was 6 (0.5%) and 5 (0.4%) for drotrecogin alfa (activated)-treated and placebo-treated patients, respectively.
L- inċidenza ta ’ fsada fis- CNS matul il- perijodu ta ’ studju ta ’ 28 ġurnata kienet ta ’ 6 (0. 5%) u ta ’ 5 (0. 4%) fil- pazjenti li ħadu drotrecogin alfa (attivat) u l - plaċebo, rispettivament.