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ČESKÁ426804001075194139184242
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SLOVENSKÁ764804001074283142189234293335381439
FARMACIE1224804001074291139211266317337381
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slov.1891804001073452101141153
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MEDICAMENTA42620009866110168191241296364408465510558
NOVA100220009855114163213
Atrasentan:425320095477195132162202245269306349363
nová8053200954387123160
molekula98232009566109127167201244261298
v129732009536
léčbě1351320095175693137178
IgA15463200951761108
nefropatie16723200954282104128171216253277294334
a202332009537
jiných2077320095173477112147190
glomerulopatií22853200954360104170209233277294337382419444461478
zmírnění4253980010737113132160210256306325
účinku779398001074890110159198248
atrasentanu105639800107416997140175221271299341391440
na1525398001074890
retenci1644398001072771100144194236256
tekutin1928398001072872112162191211261
může22173980010775124162206
snížit2451398001073484103141162191
i26713980010719
riziko271139800107274886106146194
kardiovaskulárních425412001073881108156175224265307340379427447488515564583624672
komplikací,1115412001073886160210230249288330372391407
které1540412001073869112139183
byly1741412001074989109150
více1909412001074060101144
pozorovány2071412001074999135182210257298340389428
u25174120010747
pacientů2585412001074991133152196245272320
s4254260010734
diabetem480426001074969110160206235278353
ve854426001074185
studii961426001073363112162182201
SONAR11844260010742103162215261
(12).1466426001072465103126141
Klinické4254510013971106141210244297363423
studie875451001394994163233268329
s12314510013949
atrasentanem13064510013961105153214266328397442505573635734
V5654680010746
současné631468001073482131171213246294339
době996468001074998148193
probíhají1216468001075077124175194244285304323
tři156546800107285574
studie1666468001073362111160179223
s19164680010733
atrasentanem.196946800107416995137171215264291332381425499515
Dvě25114680010758101144
studie2682468001073363111161179223
v4254820010741
indikaci485482001071967116135173215256274
IgA780482001071968121
nefropatie,921482001074893116144191241283310329372387
jedna1328482001072063114162202
studie1551482001073362110160178222
v17944820010740
širší185448200107345278112131
indikaci2005482001071967116135173215255274
zahrnující2300482001073678126153201249268286326345
proteinurické2665482001075077124151194213425496001074896122141182219263
glomerulopatie707496001074968116190235261310328377427468495514558
(13).1285496001072463101122135
1.425522001235474
studie522522001234278136195222275
ALIGN8205220012363113140208278
Studie565538001074268116165184228
ALIGN810538001075292111168225
je1052538001071963
multicentrická,11325380010774121140168187227270318345371391431469511527
randomizovaná,1676538001072668116165213288306343390430472520560576
dvojitě2269538001074990138157175203246
zaslepená,2531538001073779112131175225269318358374
placebem425552001075069110150193243287361
kontrolovaná811552001073885134161188235254302343384432473
studie1309552001073362110160178222
fáze1556552001072466103146
317275520010744
u17965520010747
pacientů1863552001075091132151194243269317
s22055520010734
biopticky2258552001075069117167195214254292335
verifikovanou2617552001074184111130154174212259425566001074284134184233
IgA686566001071970124
nefropatií,837566001075095120148197248291319339358375
kteří1239566001073971115142162
jsou1428566001072053103153
v16085660010742
riziku167156600107274785105144194
progrese1892566001075179127179206250285331
přes2250566001075179123158
renoprotekci2435566001072771121171222250299327371410451470
maximálně4255800010774114154173247288307354398
tolerovanou84358000107287594138165212252293342390438
dávkou1301580001074990129168215263
RASi.15845800010746100143161177
Hlavním565594001075775116156205223296
cílem87859400107405979123197
studie1091594001073463111160179222
je1330594001071963
definovat,1410594001074892116136184232272313340357
zda1783594001073785125
přidání192559400107507695144185233251
atrasentanu219359400107416895136169213262288330377425
v26355940010740
dávce2694594001074990130169211
0,7542560800107435799139
mg/den5746080010773121152196239285
ke875608001073779
stávající969608001073361101140180198215254272
terapii125660800107286994135183201219
RASi1490608001074598139156
po1662608001074996
dobu1774608001074895143190
1321979608001074480120
týdnů2114608001072768116162208
vede2338608001073981130173
v25266080010740
porovnání2584608001074997123168207255294425622001074765
s5056220010733
přidáním55662200107487492140179225243314
placeba885622001074968107146187235275
k11756220010738
vyšší1231622001073981114145163
redukci1409622001072667116162198236254
proteinurie1678622001074874120146187205251297322340383
a20766220010740
progrese2134622001074874120168193235267310
glomerulární2459622001074866112184227252299317356382429446
filtrace4256360010724436290117158199241
u6896360010748
pacientů756636001075092132151195243270317
s10966360010733
proteinurií1149636001075077124151193212260307334353372
≥15436360010754
116086360010744
g/den.1674636001074982127171219235
Vedle1932636001074587137156200
3402154636001074489134
pacientů2310636001075092132151195243270317
zařazených2650636001073678104146183226425650001074885124170
do611650001074895
hlavní722650001074866105144192210
větve947650001074082109152194
studie1156650001073361108157174217
bylo1389650001074987106153
nezávisle1558650001074790127168206225257275318
do1891650001074996
vedlejší2002650001074183132150193211242260
větve2278650001074082108151193
zařazeno2487650001073576102142179220267315
642817650001074489
pacientů425664001074991131149192240267314
léčených755664001071963104145193231270318
SGLTi1089664001074297138174194
(14).1300664001072363101122135
Studie1452664001074167115164182225
byla1694664001074988107148
zahájena1858664001073678126166184228276316
15.219066400107448195
1.2302664001074354
20212372664001074487128167
a25556640010741
očekává2615664001074888130168210249290
se425678001073478
dokončení522678001074998136184232273315363382
18.923678001074483100
12.104267800107448297
2026.1159678001074487128170187
2.425704001235480
studie528704001234278136196222275
ASSIST8267040012363117169196249303
Studie565720001074266112160177219
ASSIST806720001075394133149188230
je1058720001072062
randomizovaná,1142720001072767113161207279296331376415454501540554
dvojitě1718720001074989134152168195235
zaslepená,1976720001073677108125167215258304343357
placebem2356720001075068106145186234277349
kontrolovaná272772000107388413115642573400107277290136175214261299
crossover742734001074065110142173220258300324
studie1084734001073361107154171213
fáze131573400107236499140
214737340010744
u15347340010748
pacientů1598734001075090128145187234259305
s19207340010734
biopticky1970734001074967113161187204243279320
verifikovanou2307734001074182107124147165201246285324371417464
IgA2788734001071967117
nefropatií425748001074891113138184232272297314331
s7777480010733
eGFR826748001074499139182
≥10297480010753
30ml/min/1,73m2,1103748001074486167184215285301347378418427468510581168174800632617067480010716
kteří1743748001073867107132149
byli1913748001075087105122
léčeni2056748001071961100141187204
stabilní2281748001073360100148165182228245
maximální25477480010773112150168239278295341358
tolerovanou42576200107287289130155199237276321367413
dávkou850762001074987124160205251
RASi1113762001074597138153
s12797620010733
anebo1327762001074186128175222
bez1561762001074992126
SGLTi.1700762001074195133166185199
Pacienti1911762001074583121137178224248265
se2188762001073475
zavedenou2276762001073675113153201242288334379
léčbou266876200107196099145192238
SGLTi425776001074298137173192
museli6417760010774121153196214231
vstupně896776001074174102149197245288
dosáhnout1208776001074997129170217265312360387
proteinurie1618776001075076122148190207254301326344387
>20287760010755
0,5g/den,2106776001074558102160192236279326340
pacienti2470776001075091131148191238264281
bez2775776001075094130
předchozí3047398001074974114161199245291324341
léčby340039800107196099146183
SGLTi3595398001074195133167186
>37933980010753
0,85385939800107435699140
g/den.4011398001074979121163209222
Pacienti4246398001074582120137178224248265
bez4523398001074992126
předchozí4662398001074973114161199245291324341
léčby501539800107196099146183
SGLTi5210398001074195133167185
byli5408398001074986103120
následně3047412001074885116132173220265307
v33664120010740
osmitýdenní3421412001074777147163189229274315361406422
run-in3855412001072671116142159204
periodě4071412001074991115132177224265
stabilizováni434841200107335998144161177193227271309347392408
léčbou476841200107196099145191236
SGLTi.5016412001074195132166184198
Před5226412001074467107154
randomizací53924120010726651103047426001074995167183218258297313
museli33734260010773119150192209225
obě3611426001074896139
skupiny3762426001073469115163180226262
pacientů4037426001075089127144186232257302
dosáhnout4352426001074995126166212258304350377
proteinurie4741426001075075120145185202248293318335377
>51304260010754
0,5519742600107435699
g/den.5303426001074979122164210224
Hlavním3187440001075777118158208227302
cílem351644000107405981125200
studie3743440001073464112163182226
bylo3996440001075091111160
zhodnocení4183440001073686135186235284326369418437
bezpečnosti4647440001075096134185231273321371405434454
a51284400010741
účinnosti5189440001074990109157206255289319338
atrasentanu304745400107416996139173218267294336385433
oproti3507454001074999127175203222
placebu3756454001075070112153196247296
u40794540010748
pacientů4147454001075193134153198247274323
s44974540010734
IgA4551454001071970123
nefropatií4701454001074994118146194245287315334353
s50814540010734
perzistující5135454001075196123163182216245294314333373392
proteinurií3047468001075077124151194212260308334353372
léčených3438468001071963104147195233273321
kombinaci3779468001073885159209228276317357376
RASi41744680010746100143162
a43554680010741
SGLTi4416468001074298138175196
(15,4631468001072464101115
16).4766468001074483105119
3.3047494001235478
studie3148494001234178136195222275
AFFINITY34454940012364116166192261289343405
Studie3187510001074268115164182226
AFFINITY3437510001075394134151208226269318
je3780510001071962
otevřená3867510001074875117157184226274314
studie4206510001073462110158176220
typu4451510001072870120168
basket4643510001075092124161204231
fáze4899510001072465102145
250685100010745
určená5137510001074974113154202242
pro5404510001075077123
pacienty3047524001075193135153198247274318
s33905240010735
proteinurickými3444524001075179127154198216265313340360401439483559578
glomerulárními4048524001075069118194239266315334375402452470545564
onemocněními,4638524001074999144219268310359404453472547566581
kteří5245524001073970113140159
při543052400107517897
léčbě3047538001071962102151195
maximální32655380010773113152170243283301348365
tolerovanou365353800107287493136161208247288335382430
dávkou4106538001074988127165211259
RASi4388538001074599141158
měli45695380010774117135153
proteinurii,4745538001075076122148190208255301327345363377
resp.5145538001072769102150164
UPCR53325380010757101151195
≥30475520010753
0,53109552001074357100
<13217552001075391
g/g3317552001074880123
(IgA345455200107244189139
nefropatie),3608552001074790112138184232272298315357378390
>40125520010753
140795520010744
g/g4137552001074880123
(fokálně427455200107244591128168186232274
segmentální4562552001073476125196239285311350368414431
glomeruloskleróza),50075520010749661131852282532993173643964324514933047566001072672106147168181
>32425660010754
0,53310566001074458101
g/g3425566001074981124
(Alportův356456600107237492140188214244290330
syndrom)3909566001073373121169194240312333
a42565660010741
glomerulární4315566001074966113186229254301319359384431449
filtraci47785660010724426087112153192209
(eGFR)5002566001072464120160203225
≥52425660010753
305310566001074386
ml/5405566001077391122
min/1,733047580001077491138170211221263305
m2.33625800010773343458000632634605800010716
Pacienti3495580001074584124142185232258276
s37905800010734
diabetickou3841580001074967107155199226244283320367414
nefropatií4274580001074992115141188237278304322339
museli46335800010773120152195214231
být4883580001075088119
léčeni5021580001071962102144191209
alespoň5249580001074159102135183231279
330475940010744
měsíce31095940010774117149167206247
SGLTi3374594001074297137172192
a35845940010741
kromě3643594001073865111185228
UPCR38895940010756100151195
>41015940010754
0,54173594001074458101
g/g4292594001074981125
splňovat4435594001073482101148195234275301
eGFR47545940010744100141184
≥49565940010754
455028594001074484
ml/min.5121594001077492124194212259274
Hlavním3187608001075675115155203221294
cílem349860800107405878122195
je3709608001072063
stanovit,3788608001073462103151199239258286302
zda4106608001073684124
podávání4247608001074998147188227268316334
atrasentanu459760800107416894136168212260287328375422
v50366080010740
denní5095608001074993141188206
dávce5318608001074889128167209
0,75304762200107435799139
mg31966220010773121
po3332622001074997
dobu3444622001074995144191
523651622001074383
týdnů3750622001072768116162208
sníží397462200107337997132151
proteinurii.4140622001074975121147188206253299324343360375
Dosud45316220010757105137183231
publikované4777622001074996144163181217263302343389432
výsledky5225622001074082114132175224261302
u30476360010747
kohorty3112636001073884131178204234276
s34036360010733
IgA3454636001071967118
nefropatií3587636001074891114140186235275301319337
potvrdily3939636001074997123166192239257274313
signifikantní426863600107335098145162185204241282329355402419
snížení470363600107337997132174221238
proteinurie4957636001074975120147188206252299324342385
po5357636001074997
6,5469636001074358
123047650001074480
i31436500010719
523181650001074485
týdnech3282650001072769117165208249296
léčby3594650001071962103151190
atrasentanem380065000107416794135167211258285325373416489
za4305650001073678
současného4399650001073381128168209241289332380427
uchování4843650001074787134182222262310328
stabilních5187650001073362102151170188236254293340
hodnot3047664001074897147195243271
glomerulární3337664001074968116190235261310328369395444463
filtrace38196640010724446390117159199242
(17,4081664001072363100106
18,420766400107448399
19).4325664001074482104117
Závěr30476890013965128189249296
Současné3187706001074291139180221255302347
studie3560706001073463111161180224
prokázaly3810706001075077124163206243286305345
účinnost4181706001074889107155204252286315
atrasentanu452270600107416996137171215264291332380428
na4977706001074889
signifikantní5092706001073452102150169193213251293341368417436
snížení304772000107338098134175222240
proteinurie3303720001074975121148189207254301326345388
jako370772000107195895141
hlavního3864720001074866106144192210259306
rizikového41867200010726458199136183222264311359
faktoru4560720001072465102132178204251
progrese4827720001074975121170196238271314
chronického51577200010739861121582062232633003423047734001074896
onemocnění3159734001074896140213261302350393441459
ledvin3635734001071962112153172219
při387173400107497594
současném3982734001073381129169210243290334407
uchování4405734001074888136184223265312331
dobrého4752734001074996146173215263311
bezpečnostního50807340010749931301802252653133613944233047748001074867117165
profilu3237748001075077124148168186234
a34967480010741
tolerance355674800107287594138165207255295338
u39197480010747
pacientů3986748001075091132151194242269317
s43287480010734
IgA4381748001071969121
nefropatií4527748001074893116144191241283310329347
a48997480010741
proteinurickými4960748001075076124151193212260307334353393431474549567
glomerulopatiemi.3047762001074968117192236263312331380430472500519563637656672
Dlouhodobý3746762001075879127176224273324372423463
efekt4235762001074468112151182
na4443762001074990
uchování4559762001074889138187227269318336
renální4922762001072770119160179227246
funkce5194762001072474122160200243
je5463762001072064
předmětem3047776001075076119169243287315357431
dosud3497776001074998131178228
probíhajících3744776001075077124174193243284303321361380420468
klinických423277600107385877125143183221264304352
studií.4603776001073463111160179198213
Obr.425640011466122160181
2.62464001145279
Design74864001075696127144189235
studie99964001073158103148167205
ALIGN122064001074885103156210
(převzato14466400107246995132170207251277321
z1783640010735
14)183464001074278100
Main5069900906096114156
stratum678990090295580117141183245
n598108009041
=655108009044
34071510800903877116
(key5001170090215694129
analyses)64511700903577113132168198236266285
Exploratory52514300903673116135177202238263304329367
SGLT2i60315300903785121154194211
stratum5861620090295580117142183246
n611171009041
=668171009044
6472817100903878
Screening115612900913873100139178221241284327
61189148009140
weeks124414800915594134173206
}9921150034180
Randomized167711900904077118161203265283316354397
1:118331290090385085
Per167913800903976101
stratum*17961380090295580117142183246275
}23721500314234180
Atrasentan24541200090456994131161199241266303345
0.7528141200090385492129
mg2958120009062105
daily30781200090427896114150
for32441200090226388
132334812000903872109
weeks347312000905492130166198
Matched256814200906096121154196234277
placebo28611420090426197131168211254
for31301420090226389
132323414200903872109
weeks335914200905492130166198
}37531170034180
Off-412311900915278104127
treatment40211280091265392131157221260304330
Follow402613800913880100120162218
up426013800914286
132293816000914076115
weeks306816000915694134173206
44006161009140
weeks406116100915594134173206
Week2227182009164102142180
36242318200913980
–2518182009137
interim25701820091196289128155175239
analysis282418200913881119139177209229260
Primary23811920090396482144181206244
Endpoint264019200903778121164206224266291
Δ2397201009046
UPCR245920100904888131171
(n264620100902161
=2723201009044
270)278320100903874111132
Week3625182009164102142180
136382018200914076116
–3952182009137
final40041820091234588126146
analysis416518200913881119139177209229260
Key364119200904077113
Secondary376919200903775110150192235272296334
Endpoint411919200903778121164206224266290
Δ3768201009046
eGFR383020100903786123163
(n400820100902161
=4085201009044
340)414520100903877116137
Off-523911400915278104127
treatment51401230091265291129154217256298324
Follow519313300913880100120162218
up525914200914286
45172163009140
weeks522716300915594134173206
Open45437700905194133175
label4734770090175496135154
Extenssion45458700903673100138180210239257299341
Atrasentan45491140090456994131161199241266303345
0.7545971230090385492128
mg4741123009062104
daily45941330090427896114150
for47601330090216388
48457514200903878
weeks466814200905592131167199
Obr.4252410011466122160181
3.623241001145177
Design746242001075696127144189235
studie996242001073157103148167204
ASSIST1216242001074887125142179220
(převzato145124200107246994131170206250276320
z17862420010735
15)183624200107427698
IgAN49326300971965114167
RASi67726300974394135154
stable8482630097315999145165206
SGLT2i54529000853580113144181196
Naive7552900085468096130165
or53229800853862
Non-stable60729800854685124147175199233273290326
AND66627900854389137
SGLT2i53232200853580115146184200
Stable7473220085345792133151187
OR69231100854784
SGLT2i124528900853580113144181196
Run-in124729600853876115138155194
Randomized170130200853872111151189248264295330370
(1:1)1830310008520536496111
(8119830700852055
weeks)126830700855287124158188207
Stratified17163380085335477113136152172191223261
by199033800853667
SGLT2i169834600853376107137173189
Status19003460085325490112150176
(Stable16343540085205273109147164196
vs.18433540085325975
Run-in)193035400853775113136153191210
Sequence226529500853570110149184223255290
AB256829500854381
Sequence226531800853570110149184223255290
BA256831800853880
Wash349430400855992119158
out366630400853877100
(1234803120085205384
weeks)357731200855287123156186203
Safety52023000085356989125148183
follow-up5151308008520597693131183205244284
(4515831600852054
weeks)522531600855287123156186203
Placebo43352780085375488121156197237
(QD)438628600852067115135
0.7541733250085365187122
mg431032500855898
Atrasentan44233250085436689124153189229252287327
(QD)439433300852067115135
Treatment41663020086375996132158218255296322
Period450230200863975101120161203
24719302008638
(2442993100086215896
weeks)440931000865389127164195215
Placebo29213290085375488121156197237
(QD)297133700852067115135
Treatment27253020086375996132158218255296322
Period306130200863975101120161203
13278302008638
(1228603100086215691
weeks)296531000865289127163195215
0.7527482760085365187122
mg288527600855898
Atrasentan29982760085436689124153189229252287327
(QD)296928400852067115135
IgAN45536800951757100149
–618368009540
IgA67336800951657100
nepropathy;78736800954276117140180221262285326358373
QD1174368009552102
–1291368009540
once-daily;134536800954082115148173215256272289322336
RASi169636800953983119134
–1845368009540
renin-angiotensin18993680095235698114155179222263303320361384417458485500542
system24553680095286189113145209
inhibitor;26793680095165798115155172196235258273
SGLT2i296636800953582115146183198
–3179368009540
sodium323336800952868109126166230
glucose34773680095405798131170197231
cotransporter37223680095337296119157198225265306329355387411
24147368009537
inhibitor41983680095175899116156173196236259