natgillin/translations-raw huggingface dataset:
Farmakodynamiske virkninger I placebokontrollerede kliniske forsøg hos patienter med svær sepsis bevirkede Xigris en anti - trombotisk effekt ved at begrænse dannelsen af trombin og forbedre den sepsisrelaterede koagulopati, som vist ved en hurtigere forbedring af markørerne for koagulation og fibrinolyse.
Pharmacodynamic Effects In placebo-controlled clinical trials in patients with severe sepsis, Xigris exerted an antithrombotic effect by limiting thrombin generation and improved sepsis-associated coagulopathy, as shown by a more rapid improvement in markers of coagulation and fibrinolysis.
Xigris forårsagede et hurtigere fald i trombotiske markører, såsom D- dimer, protrombin F1. 2 og trombin- antitrombin - niveauer samt en hurtigere stigning i protein C og antitrombinniveauer.
Xigris caused a more rapid decline in thrombotic markers such as D-dimer, prothrombin F1.2, and thrombin-antithrombin levels and a more rapid increase in Protein C and antithrombin levels.
Endvidere genetablerede Xigris det endogene fibrinolytiske potentiale, hvilket viste sig ved en hurtigere normalisering af plasminogenniveauet, og et hurtigere fald i plasminogenaktivator inhibitor- I niveauerne.
Xigris also restored endogenous fibrinolytic potential, as evidenced by a more rapid trend toward normalisation in plasminogen levels and a more rapid decline in plasminogen activator inhibitor-1 levels.
Derudover udviste patienter med svær sepsis, som blev behandlet med Xigris, et hurtigere fald i interleukin- 6 - niveauerne, en global inflammationsmarkør, svarende til en reduktion i det inflammatoriske respons.
Additionally, patients with severe sepsis treated with Xigris had a more rapid decline in interleukin-6 levels, a global marker of inflammation, consistent with a reduction in the inflammatory response.
Klinisk effekt Xigris blev undersøgt i et internationalt, fase 3, multicenter, randomiseret, dobbeltblindt, placebo - kontrolleret forsøg (PROWESS), omfattende 1690 patienter med svær sepsis.
Clinical Efficacy Xigris was studied in one Phase 3 international, multi-centre, randomised, double-blind, placebo- controlled trial (PROWESS) in 1690 patients with severe sepsis.
De patienter, som levede op til diagnosen svær sepsis havde a) kendt eller mistænkt infektion, b) kliniske tegn på en systemisk reaktion på infektion inklusiv feber eller hypotermi, leukopeni eller leukocytose, takykardi og takypnø og c) akut organ - dysfunktion.
Patients meeting the clinical diagnosis of severe sepsis had a) known or suspected infection, b) clinical evidence of systemic response to infection including fever or hypothermia, leucopenia or leucocytosis, tachycardia and tachypnoea, and c) acute organ dysfunction.
Organdysfunktion blev defineret som shock, hypotension eller behov for vasopressor - støtte på trods af adækvat væsketilskud, relativ hypoxæmi (forholdet mellem det partielle oxygentryk i arterieblodet i mm Hg og det procentvise indhold af oxygen i indåndingsluften udtrykt som decimaltal (PaO2/ FiO2 forholdet) < 250), oliguri på trods af adækvat væsketilskud, væsentligt nedsat trombocyttal og/ eller forhøjede mælkesyrekoncentrationer.
Organ dysfunction was defined as shock, hypotension or the need for vasopressor support despite adequate fluid resuscitation, relative hypoxemia (ratio of partial pressure of oxygen in arterial blood in mmHg to the percentage of oxygen in the inspired air expressed as a decimal (PaO2/ FiO2 ratio) < 250), oliguria despite adequate fluid resuscitation, marked reduction in blood platelet counts, and/ or elevated lactic acid concentrations.
4. 3 og 4. 4), patienter som ikke forventedes at overleve i 28 dage på grund af eksisterende, ikke- sepsis relaterede medicinske forhold, HIV- positive patienter, hvis seneste CD4 tal var ≤ 50/ mm3, patienter i kronisk dialyse, patienter, som havde fået foretaget knoglemarvs -, lunge -, lever -, pankreas - eller tyndtarmstransplantation, og patienter med akut klinisk pankreatitis uden kendt infektionskilde.
Exclusion criteria encompassed patients at high risk of bleeding (see sections 4.3 and 4.4), patients who were not expected to survive for 28 days due to a pre-existing, non-sepsis related medical condition, HIV positive patients whose most recent CD4 count was ≤ 50/ mm3, patients on chronic dialysis, and patients who had undergone bone marrow, lung, liver, pancreas or small bowel transplantation, and patients with acute clinical pancreatitis without a proven source of infection.
I PROWESS forsøget, blev behandling iværksat indenfor 48 timer efter det første sepsis- inducerede organsvigt.
8 In the PROWESS trial, treatment was initiated within 48 hours of onset of the first sepsis-induced organ dysfunction.
Patienterne fik en 96 timers Xigris infusion med en konstant hastighed på 24 µg/ kg/ time (n=850) eller placebo (n=840).
Patients were given a 96-hour constant rate infusion of Xigris at 24 µg/ kg/ hr (n=850) or placebo (n=840).
Efter 28 dage var den totale dødelighed 24, 7% for gruppen, som blev behandlet med Xigris, og 30, 8% for placebogruppen (p=0, 005).
At 28 days, the overall mortality rates were 24.7% for the Xigris-treated group and 30.8% for the placebo-treated group (p=0.005).
APACHE II score ≥ 25 eller mindst 2 akutte organdysfunktioner ved baseline.
Significant absolute death reduction was limited to the subgroup of patients with greater disease severity i. e. baseline APACHE II score ≥ 25 or at least 2 acute organ dysfunctions at baseline.
I subgruppen af patienter med en APACHE II score ≥ 25 ved baseline var mortaliteten 31% i Xigrisgruppen (128 ud af 414) og 44% i placebogruppen (176 ud af 403).
In the subgroup of patients with an APACHE II score ≥ 25 at baseline, the mortality was 31% in the Xigris group (128 out of 414) and 44% in the placebo group (176 out of 403).
I subgruppen af patienter med mindst 2 akutte organdysfunktioner ved baseline var mortaliteten 26, 5% i Xigrisgruppen (168 ud af 634) og 33, 9% i placebogruppen (216 ud af 637).
In the subgroup of patients with at least 2 acute organ dysfunctions at baseline, the mortality was 26.5% in the Xigris group (168 out of 634) and 33.9% in the placebo group (216 out of 637).
Der blev ikke observeret nogen signifikant reduktion i dødeligheden hos subgruppen af patienter, der havde mindre end 2 akutte organdys - funktioner.
No significant death reduction was observed in the subgroup of patients with less than 2 acute organ dysfunctions at baseline.
PROWESS opfølgningsundersøgelse Overlevelsesstatus er blevet vurderet i en opfølgningsundersøgelse med overlevende fra PROWESS - studiet.
PROWESS Follow-up Study Survival status was assessed in a follow-up study of PROWESS survivors.
Overlevelsesstatus for hospitalsindlagte samt overlevelsesstatus efter 3 måneder var rappor - teret for henholdsvis 98% og 94% af de 1690 PROWESS- patienter.
In-hospital and 3 month survival status was reported for 98% and 94% of the 1690 PROWESS subjects respectively.
For den samlede population var mortaliteten for hospitalsindlagte signifikant lavere for patienter i behandling med Xigris end for placebo (29, 4% versus 34, 6%, p=0, 023).
34.6%; p=0.023).
Overlevelse efter 3 måneder var ligeledes bedre for Xigris - gruppen i forhold til placebo (Log- Rank p=0, 048).
Survival through 3 months was also better in the Xigris group compared to placebo (log rank p=0.048).
Yderligere klinisk erfaring I et internationalt, enkelt- arm, open- label klinisk fase 3b forsøg (ENHANCE) modtog 2378 voksne patienter med svær sepsis drotrcogin alfa (aktiveret).
Further Clinical Experience In a Phase 3b international, single-arm, open-label clinical trial (ENHANCE), 2378 adult patients with severe sepsis received drotrecogin alfa (activated).
Patienterne fik drotrecogin alfa (aktiveret) indenfor 48 timer efter, at det første sepsis - inducerede organsvigt var indtrådt.
Patients received drotrecogin alfa (activated) within 48 hours of onset of the first sepsis- induced organ dysfunction.
I fase 3b forsøget var mortaliteten 25, 3% efter 28 dage.
At 28 days, the mortality rate in the Phase 3b study was 25.3%.
I et randomiseret, dobbeltblindt, placebokontrolleret klinisk forsøg (ADDRESS) blev der i alt indrul - leret 2640 voksne patienter med svær sepsis og en lav dødelighedsrisiko (APACHE II < 25 eller kun med et sepsis- induceret organsvigt).
A total of 2640 adult patients with severe sepsis who were at low risk of death (e. g. patients with APACHE II < 25 or with only one sepsis-induced organ failure) were enrolled in a randomised, double- blind, placebo-controlled trial (ADDRESS).
Forsøget blev standset efter en interim analyse fordi der var ringe sandsynlighed for at påvise en signifikant forskel på 28- dages dødeligheden ved afslutningen af 9 forsøget.
The trial was stopped after an interim analysis due to a low likelihood of demonstrating a significant difference in 28-day mortality by the end of the trial.
Der blev indrulleret 872 patienter med flere organ dysfunktioner i ADDRESS- forsøget.
The ADDRESS trial did enrol 872 patients with multiple organ dysfunction.
Sammenlignet med patienter med flere organ dysfunktioner, der var indrulleret i PROWESS havde de tilsvarende patienter i ADDRESS haft organ dysfunktion i længere tid inden de modtog forsøgs - medicin (median 25 mod 18 timer).
Compared to multiple organ dysfunction patients in PROWESS, those in ADDRESS had organ dysfunction for longer prior to receiving study drug (median 25 vs.
Samtidig havde de lavere APACHE II score (median 20 mod 25), og de havde en større sandsynlighed for blot to organ dysfunktioner (76% mod 43%).
43%).
Dødeligheden for patienter med flere organ dysfunktioner i ADDRESS efter 28 dage var henholdsvis 20, 7% og 21, 9% af de drotrecogin alfa (aktiveret) - behandlede og placebobehandlede patienter.
At 28 days, the mortality rates for multiple organ dysfunction patients in ADDRESS were 20.7% versus 21.9% for drotrecogin alfa (activated)-treated and placebo-treated patients, respectively.
Dødeligheden under indlæggelse var henholdsvis 23, 1% og 25, 3%.
In-hospital mortality rates were 23.1% and 25.3% respectively.
I undergruppen med to organ dysfunktioner var resultaterne sammenlignelige med dem, som blev fundet i PROWESS- forsøget.
In the subgroup with two organ dysfunctions, the results were similar to those seen in the PROWESS trial.
Behandlingseffekten var mest tydelig på sites, som indrullerede større mængder af patienter i de placebokontrollerede forsøg.
9 In placebo controlled clinical trials, the treatment effect was most evident at sites enrolling larger numbers of patients.
Plasma - koncentrationer af endogent aktiveret protein C hos raske forsøgspersoner og hos patienter med svær sepsis ligger normalt under detektionsgrænsen (< 5 ng/ ml) og påvirker ikke signifikant de farmako - kinetiske egenskaber af drotrecogin alfa (aktiveret).
Plasma concentrations of endogenous Activated Protein C in healthy subjects and patients with severe sepsis are usually below detection limits (< 5 ng/ ml) and do not significantly influence the pharmacokinetic properties of drotrecogin alfa (activated).
Hos raske forsøgspersoner er mere end 90% af steady state koncentrationen opnået inden for 2 timer efter påbegyndelsen af en Xigrisinfusion med konstant hastighed.
In healthy subjects, greater than 90% of the steady state condition is attained within 2 hours following the start of a constant-rate intravenous infusion of Xigris.
Efter afslutningen af infusionen falder plasmakoncentrationen af drotrecogin alfa (aktiveret) i to faser omfattende en hurtig første fase (t½ α = 13 minutter) og en langsommere anden fase (t½ β = 1, 6 time).
Following the completion of an infusion, the decline in plasma drotrecogin alfa (activated) concentrations is biphasic and is comprised of a rapid initial phase (t1/ 2 α =13 minutes) and a slower second phase (t1/ 2 β =1.6 hours).
80% af arealet under plasmakoncentrationskurven og styrer den initiale hurtige stigning i plasmakoncentrationen af drotrecogin alfa (aktiveret) mod steady state.
The short half-life of 13 minutes accounts for approximately 80% of the area under the plasma concentration curve and governs the initial rapid accrual of plasma drotrecogin alfa (activated) concentrations towards the steady-state.
Steady state plasmakoncentrationerne af drotrecogin alfa (aktiveret) er proportionale med infusionshastigheden i intervallet 12 µg/ kg/ time til 48 µg/ kg/ time.
Plasma drotrecogin alfa (activated) steady-state concentrations are proportional to the infusion rate over a range of infusion rates from 12 µg/ kg/ hr to 48 µg/ kg/ hr.
Den gennemsnitlige steady state plasmakoncentration af drotrecogin alfa (aktiveret) hos raske forsøgspersoner, der får 24 µg/ kg/ time, er 72 ng/ ml.
The mean steady-state plasma concentration of drotrecogin alfa (activated) in healthy subjects receiving 24 µg/ kg/ hr is 72 ng/ ml.
Hos patienter med svær sepsis medførte infusion af drotrecogin alfa (aktiveret) fra 12 µg/ kg/ time til 30 µg/ kg/ time hurtigt steady state plasmakoncentrationer, som var proportionale med infusions - hastighederne.
In patients with severe sepsis, infusion of drotrecogin alfa (activated) from 12 µg/ kg/ hr to 30 µg/ kg/ hr rapidly produced steady-state plasma concentrations that were proportional to infusion rates.
I det kliniske fase 3 forsøg blev farmakokinetikken af drotrecogin alfa (aktiveret) evalueret hos 342 patienter med svær sepsis, som fik administreret 24 µg/ kg/ time, kontinuerligt infunderet over 96 timer.
In the Phase 3 trial, the pharmacokinetics of drotrecogin alfa (activated) were evaluated in 342 patients with severe sepsis administered a 96-hour continuous infusion at 24 µg/ kg/ hr.
41, 8 l/ time hos patienter med sepsis mod 28, 1 l/ time hos raske forsøgspersoner.
The plasma clearance of drotrecogin alfa (activated) is approximately 41.8 l/ hr in sepsis patients as compared with 28.1 l/ hr in healthy subjects.
Hos patienter med svær sepsis blev plasmaclearance af drotrecogin alfa (aktiveret) signifikant nedsat ved nyresvækkelse og lever dysfunktion, men forskellen i clearance (< 30%) berettiger ikke til en justering af dosis.
In patients with severe sepsis, the plasma clearance of drotrecogin alfa (activated) was significantly decreased by renal impairment and hepatic dysfunction, but the magnitude of the differences in clearance (< 30%) does not warrant any dosage adjustment.
10 Xigris har hverken været undersøgt i karcinogenicitets - eller reproduktionsforsøg hos dyr.
Carcinogenicity studies and animal reproduction studies have not been conducted with Xigris.
4. 6).
However, with respect to the latter, the potential risk for humans being unknown, Xigris should not be used during pregnancy unless clearly necessary (see section 4.6).
Saccharose Natriumchlorid Natriumcitrat Citronsyre Saltsyre Natrumhydroxid
Sucrose Sodium chloride Sodium citrate Citric acid Hydrochloric acid Sodium hydroxide
Pulver i type I- hætteglas.
Powder in Type I glass vial.
2 mg/ ml drotrecogin alfa (aktiveret).
Prior to administration, 20 mg vials of Xigris must be reconstituted with 10 ml of Sterile Water for Injection, resulting in a solution with a concentration of approximately 2 mg/ ml drotrecogin alfa (activated).
11 4.
4.
Opløsningen af rekonstitueret Xigris skal yderligere fortyndes med steril natriumchlorid injektionsvæske 0, 9% til en endelig koncentration mellem 100 µg/ ml og 200 µg/ ml.
The solution of reconstituted Xigris must be further diluted with sterile 0.9% Sodium Chloride Injection to a final concentration of between 100 µg/ ml and 200 µg/ ml.
Tilsæt det rekonstituerede drotrecogin alfa (aktiveret) til en forberedt infusionspose med steril natriumchlorid injektionsvæske 0, 9%.
Add the reconstituted drotrecogin alfa (activated) into a prepared infusion bag of sterile 0.9% Sodium Chloride Injection.
Når det rekonstituerede drotrecogin alfa (aktiveret) tilsættes infusionsposen, skal strålen rettes mod siden af infusionsposen for at minimere uro i opløsningen.
When adding the reconstituted drotrecogin alfa (activated) into the infusion 11 bag, direct the stream to the side of the bag to minimise the agitation of the solution.
Rekonstitueret Xigris skal fortyndes i en infusionspose indeholdende steril natriumchlorid injektionsvæske 0, 9% til en færdig koncentration på mellem 100 µg/ ml og 200 µg/ ml.
The solution of reconstituted Xigris should be diluted into an infusion bag containing sterile 0.9% Sodium Chloride Injection to a final concentration of between 100 µg/ ml and 200 µg/ ml.
5 ml/ time.
When administering drotrecogin alfa (activated) at low flow rates (less than approximately 5 ml/ hr), the infusion set must be primed for approximately 15 minutes at a flow rate of approximately 5 ml/ hr.
De ENESTE andre opløsninger, som må administreres gennem den samme slange, er natriumchlorid injektionsvæske 0, 9%, Ringer- laktat infusionsvæske, glukose eller glukose - / saltblandinger.
The ONLY other solutions that can be administered through the same line are 0.9% Sodium Chloride Injection, Lactated Ringer’ s Injection, Dextrose or Dextrose and Saline mixtures.
Undgå at udsætte opløsninger af drotrecogin alfa (aktiveret) for varme og/ eller direkte sollys.
Avoid exposing drotrecogin alfa (activated) solutions to heat and/ or direct sunlight.
Eli Lilly Nederland B. V., Grootslag 1- 5, 3991 RA, Houten, Holland
Eli Lilly Nederland B. V., Grootslag 1-5, 3991 RA, Houten, The Netherlands
22. august 2002 Dato for seneste fornyelse:
Date of latest renewal:
Yderligere information om dette lægemiddel er tilgængelig på Det europæiske Lægemiddelagenturs (EMEAs) hjemmeside http: // www. emea. europa. eu /
Detailed information on this product is available on the website of the European Medicines Agency (EMEA): http: / /www. emea. europa. eu/ 12 1.
Efter rekonstitution med 2, 5 ml vand til injektionsvæsker indeholder hver ml 2 mg drotrecogin alfa (aktiveret).
After reconstitution with 2.5 ml of Water for Injection each ml contains 2 mg of Drotrecogin alfa (activated).
17 mg natrium.
Each vial contains approximately 17 mg sodium.
Forsøget blev stoppet efter, at 477 patienter havde modtaget forsøgsbehandlingen, grundet manglende formål med at fortsætte.
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 paediatric patients and showed a higher rate of central nervous system bleeding in the Xigris versus
Forsøget viste en højere hyppighed af blødning i centralnervesystemet hos gruppen, som modtog Xigris, sammenlignet med placebo - 14 gruppen.
13 placebo group.
Hyppigheden af alvorlig blødningstilfælde med Xigris var højere hos patienter med
The incidence of serious bleeding events with Xigris was higher in patients with recent [within 30 days] surgery than in “ medical” patients without surgery (see section 4.8).
Blødningsrisikoen bør tages i betragtning, når man vurderer risk- benefit for individuelle patienter.
14 Bleeding risk should be taken into account when considering the risk benefit for individual patients.
Immunogenicitet I kliniske studier for svær sepsis er frekvensen af anti- human aktiveret protein C IgA/ IgG/ IgM antistoffer eller neutraliserende antistoffer lav hos voksne patienter og er omtrent ens for de testede drotrecogin alfa (aktiveret) - og placebobehandlede patienter.
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.
Der var ingen tegn på at de påviste antistoffer repræsenterede et specifikt immunrespons til drotrecogin alfa (aktiveret) - behandling.
There was no evidence that the antibodies detected represented a specific immune response to drotrecogin alfa (activated) therapy.
16 Data fra et placebokontrolleret klinisk forsøg har ikke fastslået effekten af Xigris hos børn, som lider af svær sepsis, akut infektion, systemisk inflammation samt respiratorisk og kardiovaskulær organ dysfunktion.
15 Data from a placebo-controlled clinical trial did not establish efficacy of Xigris in paediatric patients suffering from severe sepsis, acute infection, systemic inflammation and respiratory and cardiovascular organ dysfunction.
17 mg natrium pr. hætteglas.
This medicinal product contains approximately 17 mg sodium per vial.
I forsøget påvirkede profylaktisk heparinbehandling ikke i nævneværdig grad dødeligheden (heparin 28, 3% mod placebo 31, 9%) i den samlede ITT population, og heparin 30, 3% mod placebo 26, 9% hos de patienter med multipel organdysfunktion, som havde modtaget behandling indenfor 24 timer efter deres første sepsis - inducerede organ dysfunktion (n=890).
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)).
17 Ikke relevant.
Not relevant.
Det internationale fase 3, multicenter, randomiserede, dobbeltblinde, placebokontrollerede kliniske forsøg (PROWESS) omfattede 850 drotrecogin alfa (aktiveret) - behandlede og 840 placebobehandlede patienter.
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.
Under infusionsperioden i PROWESS og ENHANCE var hyppigheden af alvorlig blødningstilfælde med Xigris numerisk højere hos patienter med nylig (indenfor 30 dage) operation, end hos patienter, der ikke var opereret (PROWESS:
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:
Samtidig var hyppigheden af CNS- blødninger 1, 5% i løbet af den 28 - dages forsøgsperiode.
18 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%.
19 4. 9 Overdosering
4.9 Overdose
Endvidere genetablerede Xigris det endogene fibrinolytiske potentiale, hvilket viste sig ved en hurtigere normalisering af plasminogenniveauet, og et hurtigere fald i plasminogenaktivator inhibitor- I niveauerne.
Additionally, patients with severe
Derudover udviste patienter med svær sepsis, som blev behandlet med Xigris, et hurtigere fald i interleukin- 6 - niveauerne, en global inflammationsmarkør, svarende til en reduktion i det inflammatoriske respons.
19 sepsis treated with Xigris had a more rapid decline in interleukin-6 levels, a global marker of inflammation, consistent with a reduction in the inflammatory response.
I PROWESS forsøget, blev behandling iværksat indenfor 48 timer efter det første sepsis- inducerede organsvigt.
In the PROWESS trial, treatment was initiated within 48 hours of onset of the first sepsis-induced organ dysfunction.
Der blev ikke observeret nogen signifikant reduktion i dødeligheden hos subgruppen af patienter, der havde mindre end 2 akutte organ - dysfunktioner.
No significant death reduction was observed in the subgroup of patients with less than 2 acute organ dysfunctions at baseline.
Overlevelse efter 3 måneder var ligeledes bedre for Xigrisgruppen i forhold til placebo (Log- Rank p=0, 048).
Survival through 3 months was also better in the Xigris group compared to placebo (log rank p=0.048).
Yderligere klinisk erfaring I et internationalt, enkelt- arm, open- label klinisk fase 3b forsøg (ENHANCE) modtog 2378 voknse patienter med svær sepsis drotrcogin alfa (aktiveret).
20 Further Clinical Experience In a Phase 3b international, single-arm, open-label clinical trial (ENHANCE), 2378 adult patients with severe sepsis received drotrecogin alfa (activated).