• Je něco špatně v tomto záznamu ?

Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial

MA. Riedl, V. Grivcheva-Panovska, D. Moldovan, J. Baker, WH. Yang, BM. Giannetti, A. Reshef, S. Andrejevic, RF. Lockey, R. Hakl, S. Kivity, JR. Harper, A. Relan, M. Cicardi,

. 2017 ; 390 (10102) : 1595-1602. [pub] 20170725

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu klinické zkoušky, fáze II, srovnávací studie, časopisecké články, multicentrická studie, randomizované kontrolované studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc18033802
E-zdroje Online Plný text

NLK ProQuest Central od 1992-01-04 do Před 3 měsíci
Nursing & Allied Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Health & Medicine (ProQuest) od 1992-01-04 do Před 3 měsíci
Family Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Psychology Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Health Management Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Public Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci

Odkazy

PubMed 28754491
DOI 10.1016/s0140-6736(17)31963-3
Knihovny.cz E-zdroje

BACKGROUND: Hereditary angio-oedema is a recurrent, oedematous disorder caused by deficiency of functional C1 inhibitor. Infusions of plasma-derived C1 esterase inhibitor deter attacks of hereditary angio-oedema, but the prophylactic effect of recombinant human C1 esterase inhibitor has not been rigorously studied. We aimed to assess the efficacy of recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema. METHODS: We conducted this phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial at ten centres in Canada, the Czech Republic, Israel, Italy, Macedonia, Romania, Serbia, and the USA. We enrolled patients aged 13 years or older with functional C1-inhibitor concentrations of less than 50% of normal and a history of four or more attacks of hereditary angio-oedema per month for at least 3 months before study initiation. Patients were randomly assigned centrally (1:1:1:1:1:1), via an interactive response technology system with fixed allocation, to receive one of six treatment sequences. During each sequence, patients received intravenous recombinant human C1 esterase inhibitor (50 IU/kg; maximum 4200 IU) twice weekly, recombinant human C1 esterase inhibitor once weekly and placebo once weekly, and placebo twice weekly, each for 4 weeks with a 1 week washout period between crossover. All patients, investigators, and study personnel who participated in patient care were masked to group allocation during the study. The primary efficacy endpoint was the number of attacks of hereditary angio-oedema observed in each 4 week treatment period. Attack symptoms were recorded daily. The primary efficacy analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one injection of study medication. This study is registered with ClinicalTrials.gov, number NCT02247739. FINDINGS: Between Dec 29, 2014, and May 3, 2016, we enrolled 35 patients, of whom 32 (91%) underwent randomisation (intention-to-treat population) and 26 (81%) completed the study. The mean number of attacks of hereditary angio-oedema over 4 weeks was significantly reduced with recombinant human C1 esterase inhibitor twice weekly (2·7 attacks [SD 2·4]) and once weekly (4·4 attacks [3·2]) versus placebo (7·2 attacks [3·6]), with mean differences of -4·4 attacks (p<0·0001) and -2·8 attacks (p=0·0004), respectively. We recorded adverse events in ten (34%) of 29 patients given twice-weekly recombinant human C1 esterase inhibitor, 13 (45%) of 29 patients given the once-weekly regimen, and eight (29%) of 28 patients given placebo. Headache (twice-weekly treatment) and nasopharyngitis (once-weekly treatment) were the most common adverse events. Two (7%) adverse events (fatigue and headache) were deemed possibly related to treatment with recombinant human C1 esterase inhibitor, but both resolved without additional treatment. No thrombotic or thromboembolic events, systemic allergic reactions (including anaphylaxis), or neutralising antibodies were reported. INTERPRETATION: Prophylaxis with recombinant human C1 esterase inhibitor provided clinically relevant reductions in frequency of hereditary angio-oedema attacks and was well tolerated. In view of the pharmacokinetic profile of recombinant human C1 esterase inhibitor, our results suggest that efficacy of C1-inhibitor replacement therapy might not be a direct function of plasma trough concentrations of C1 inhibitor. FUNDING: Pharming Technologies.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18033802
003      
CZ-PrNML
005      
20181016110247.0
007      
ta
008      
181008s2017 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1016/S0140-6736(17)31963-3 $2 doi
035    __
$a (PubMed)28754491
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Riedl, Marc A $u Department of Medicine, University of California, San Diego, San Diego, CA, USA. Electronic address: mriedl@ucsd.edu.
245    10
$a Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial / $c MA. Riedl, V. Grivcheva-Panovska, D. Moldovan, J. Baker, WH. Yang, BM. Giannetti, A. Reshef, S. Andrejevic, RF. Lockey, R. Hakl, S. Kivity, JR. Harper, A. Relan, M. Cicardi,
520    9_
$a BACKGROUND: Hereditary angio-oedema is a recurrent, oedematous disorder caused by deficiency of functional C1 inhibitor. Infusions of plasma-derived C1 esterase inhibitor deter attacks of hereditary angio-oedema, but the prophylactic effect of recombinant human C1 esterase inhibitor has not been rigorously studied. We aimed to assess the efficacy of recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema. METHODS: We conducted this phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial at ten centres in Canada, the Czech Republic, Israel, Italy, Macedonia, Romania, Serbia, and the USA. We enrolled patients aged 13 years or older with functional C1-inhibitor concentrations of less than 50% of normal and a history of four or more attacks of hereditary angio-oedema per month for at least 3 months before study initiation. Patients were randomly assigned centrally (1:1:1:1:1:1), via an interactive response technology system with fixed allocation, to receive one of six treatment sequences. During each sequence, patients received intravenous recombinant human C1 esterase inhibitor (50 IU/kg; maximum 4200 IU) twice weekly, recombinant human C1 esterase inhibitor once weekly and placebo once weekly, and placebo twice weekly, each for 4 weeks with a 1 week washout period between crossover. All patients, investigators, and study personnel who participated in patient care were masked to group allocation during the study. The primary efficacy endpoint was the number of attacks of hereditary angio-oedema observed in each 4 week treatment period. Attack symptoms were recorded daily. The primary efficacy analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one injection of study medication. This study is registered with ClinicalTrials.gov, number NCT02247739. FINDINGS: Between Dec 29, 2014, and May 3, 2016, we enrolled 35 patients, of whom 32 (91%) underwent randomisation (intention-to-treat population) and 26 (81%) completed the study. The mean number of attacks of hereditary angio-oedema over 4 weeks was significantly reduced with recombinant human C1 esterase inhibitor twice weekly (2·7 attacks [SD 2·4]) and once weekly (4·4 attacks [3·2]) versus placebo (7·2 attacks [3·6]), with mean differences of -4·4 attacks (p<0·0001) and -2·8 attacks (p=0·0004), respectively. We recorded adverse events in ten (34%) of 29 patients given twice-weekly recombinant human C1 esterase inhibitor, 13 (45%) of 29 patients given the once-weekly regimen, and eight (29%) of 28 patients given placebo. Headache (twice-weekly treatment) and nasopharyngitis (once-weekly treatment) were the most common adverse events. Two (7%) adverse events (fatigue and headache) were deemed possibly related to treatment with recombinant human C1 esterase inhibitor, but both resolved without additional treatment. No thrombotic or thromboembolic events, systemic allergic reactions (including anaphylaxis), or neutralising antibodies were reported. INTERPRETATION: Prophylaxis with recombinant human C1 esterase inhibitor provided clinically relevant reductions in frequency of hereditary angio-oedema attacks and was well tolerated. In view of the pharmacokinetic profile of recombinant human C1 esterase inhibitor, our results suggest that efficacy of C1-inhibitor replacement therapy might not be a direct function of plasma trough concentrations of C1 inhibitor. FUNDING: Pharming Technologies.
650    _2
$a mladiství $7 D000293
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a hereditární angioedémy $x krev $x prevence a kontrola $7 D054179
650    _2
$a inhibiční protein komplementu C1 $x škodlivé účinky $x farmakokinetika $x terapeutické užití $7 D050718
650    _2
$a klinické křížové studie $7 D018592
650    _2
$a vztah mezi dávkou a účinkem léčiva $7 D004305
650    _2
$a dvojitá slepá metoda $7 D004311
650    _2
$a rozvrh dávkování léků $7 D004334
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé $7 D006801
650    _2
$a intravenózní infuze $7 D007262
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a metabolická clearance $x fyziologie $7 D008657
650    _2
$a lidé středního věku $7 D008875
650    _2
$a rekombinantní proteiny $x škodlivé účinky $x krev $x farmakokinetika $x terapeutické užití $7 D011994
650    _2
$a výsledek terapie $7 D016896
650    _2
$a mladý dospělý $7 D055815
655    _2
$a klinické zkoušky, fáze II $7 D017427
655    _2
$a srovnávací studie $7 D003160
655    _2
$a časopisecké články $7 D016428
655    _2
$a multicentrická studie $7 D016448
655    _2
$a randomizované kontrolované studie $7 D016449
700    1_
$a Grivcheva-Panovska, Vesna $u Clinic of Dermatology, Medical University Skopje, Skopje, Macedonia.
700    1_
$a Moldovan, Dumitru $u MediQuest Clinical Research, Sangeorgiu de Mures, Romania.
700    1_
$a Baker, James $u Baker Allergy Asthma Dermatology, Lake Oswego, OR, USA.
700    1_
$a Yang, William H $u Ottawa Allergy Research Corporation, Ottawa, ON, Canada; University of Ottawa Medical School, Ottawa, ON, Canada.
700    1_
$a Giannetti, Bruno M $u Department of Operations, Pharming Group, Leiden, Netherlands.
700    1_
$a Reshef, Avner $u Sheba Medical Center, University of Tel Aviv, Tel-Hashomer, Israel.
700    1_
$a Andrejevic, Sladjana $u Clinical Center of Serbia, Belgrade, Serbia.
700    1_
$a Lockey, Richard F $u Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
700    1_
$a Hakl, Roman $u St Anne's University Hospital in Brno, Czech Republic.
700    1_
$a Kivity, Shmuel $u The Tel Aviv Medical Center, Tel Aviv, Israel.
700    1_
$a Harper, Joseph R $u Department of Clinical Research and Medical Affairs, Pharming Healthcare, Berkeley Heights, NJ, USA.
700    1_
$a Relan, Anurag $u Department of Clinical Research and Medical Affairs, Pharming Healthcare, Berkeley Heights, NJ, USA.
700    1_
$a Cicardi, Marco $u Dipartimento di Scienze Biomediche e Cliniche Luigi Sacco, Universita degli Studi di Milano, Milan, Italy.
773    0_
$w MED00010161 $t Lancet (London, England) $x 1474-547X $g Roč. 390, č. 10102 (2017), s. 1595-1602
856    41
$u https://pubmed.ncbi.nlm.nih.gov/28754491 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20181008 $b ABA008
991    __
$a 20181016110745 $b ABA008
999    __
$a ok $b bmc $g 1340302 $s 1030796
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 390 $c 10102 $d 1595-1602 $e 20170725 $i 1474-547X $m Lancet $n Lancet $x MED00010161
LZP    __
$a Pubmed-20181008

Najít záznam

Citační ukazatele

Možnosti archivace