Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial.
Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial.
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DOI：
10.1007/s00134-021-06537-5
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发表时间：
2021-11
影响因子：
38.9
通讯作者：
AdrenOSS-2 study participants
中科院分区：
文献类型：
--
作者：
Laterre PF;Pickkers P;Marx G;Wittebole X;Meziani F;Dugernier T;Huberlant V;Schuerholz T;François B;Lascarrou JB;Beishuizen A;Oueslati H;Contou D;Hoiting O;Lacherade JC;Chousterman B;Pottecher J;Bauer M;Godet T;Karakas M;Helms J;Bergmann A;Zimmermann J;Richter K;Hartmann O;Pars M;Mebazaa A;AdrenOSS-2 study participants
研究Adrecizumab（一种人源化单克隆肾上腺髓质素抗体）在肾上腺髓质素水平高的脓毒性休克患者中的安全性和耐受性。单次输注adreczumab（2或4 mg/kg b.w.）的2a期、双盲、随机、安慰剂对照生物标志物指导试验与安慰剂相比。肾上腺髓质素高于70 pg/mL、因感染性休克开始血管加压药< 12小时的患者符合资格。随机化比例为1：1：2。记录主要安全性（90天死亡率、治疗后出现的不良事件（TEAE））和耐受性（药物中断、血流动力学）终点。疗效终点包括脓毒症支持指数（SSI，反映无呼吸机和休克存活天数）、序贯相关器官衰竭评估（SOFA）变化和28天死亡率。入组了301例患者（血管加压药开始后中位时间为8.5 h）。Adrecizumab耐受性良好（一次中断，无血流动力学改变），治疗组之间TEAE的频率和严重程度无差异（3级或以上TEAE：Adrecizumab组为70.5%，安慰剂组为71.1%），90天死亡率也无差异。adrecizumab和安慰剂之间SSI变化的差异为0.72（CI-1.93-0.49，p = 0.24）。在各种次要终点中，与安慰剂组相比，Adrecizumab联合治疗组的Δ SOFA评分（定义为最大SOFA与最小SOFA）更明显[差异为0.76（95% CI 0.18-1.35）; p = 0.007]。28-adrecizumab组的日死亡率为23.9%，安慰剂组为27.7%，风险比为0.84（95%置信区间为0.53-1.31，对数秩p = 0.44）。总体而言，我们成功地完成了一项随机试验，评估了选择具有疾病相关生物标志物的患者入组。使用两种剂量的肾上腺髓质素抗体adrecizumab没有明显的危害信号;然而，需要进一步的随机对照试验来证实这种药物在脓毒性休克患者中的疗效和安全性。在线版本包含补充材料，可通过10.1007/s 00134 -021-06537-5获得。
Investigate safety and tolerability of adrecizumab, a humanized monoclonal adrenomedullin antibody, in septic shock patients with high adrenomedullin. Phase-2a, double-blind, randomized, placebo-controlled biomarker-guided trial with a single infusion of adrecizumab (2 or 4 mg/kg b.w.) compared to placebo. Patients with adrenomedullin above 70 pg/mL, < 12 h of vasopressor start for septic shock were eligible. Randomization was 1:1:2. Primary safety (90-day mortality, treatment emergent adverse events (TEAE)) and tolerability (drug interruption, hemodynamics) endpoints were recorded. Efficacy endpoints included the Sepsis Support Index (SSI, reflecting ventilator- and shock-free days alive), change in Sequential-related Organ Failure Assessment (SOFA) and 28-day mortality. 301 patients were enrolled (median time of 8.5 h after vasopressor start). Adrecizumab was well tolerated (one interruption, no hemodynamic alteration) with no differences in frequency and severity in TEAEs between treatment arms (TEAE of grade 3 or higher: 70.5% in the adrecizumab group and 71.1% in the placebo group) nor in 90-day mortality. Difference in change in SSI between adrecizumab and placebo was 0.72 (CI −1.93–0.49, p = 0.24). Among various secondary endpoints, delta SOFA score (defined as maximum versus minimum SOFA) was more pronounced in the adrecizumab combined group compared to placebo [difference at 0.76 (95% CI 0.18–1.35); p = 0.007]. 28-day mortality in the adrecizumab group was 23.9% and 27.7% in placebo with a hazard ratio of 0.84 (95% confidence interval 0.53–1.31, log-rank p = 0.44). Overall, we successfully completed a randomized trial evaluating selecting patients for enrolment who had a disease-related biomarker. There were no overt signals of harm with using two doses of the adrenomedullin antibody adrecizumab; however, further randomized controlled trials are required to confirm efficacy and safety of this agent in septic shock patients. The online version contains supplementary material available at 10.1007/s00134-021-06537-5.
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DOI：
10.1186/s13054-017-1609-1
发表时间：
2017-02-24
期刊：
Critical care (London, England)
影响因子：
--
作者：
de Grooth HJ;Geenen IL;Girbes AR;Vincent JL;Parienti JJ;Oudemans-van Straaten HM
通讯作者：
Oudemans-van Straaten HM
影响因子：
8.3
作者：
Hofbauer, KH;Schoof, E;Sandner, P
通讯作者：
Sandner, P
影响因子：
2.3
作者：
Karpinich NO;Hoopes SL;Kechele DO;Lenhart PM;Caron KM
通讯作者：
Caron KM
影响因子：
120.7
作者：
Singer, Mervyn;Deutschman, Clifford S.;Angus, Derek C.
通讯作者：
Angus, Derek C.
影响因子：
38.9
作者：
Harhay, Michael O.;Casey, Jonathan D.;Mebazaa, Alexandre
通讯作者：
Mebazaa, Alexandre