Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome.
Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome.
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DOI：
10.1136/gut.2010.218271
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发表时间：
2011-07
期刊：
影响因子：
24.5
通讯作者：
O'Keefe SJ
中科院分区：
文献类型：
--
作者：
Jeppesen PB;Gilroy R;Pertkiewicz M;Allard JP;Messing B;O'Keefe SJ
Teduglutide是一种GLP-2类似物，可通过促进粘膜修复和生长以及减少胃排空和分泌来恢复肠道结构和功能完整性，从而增加短肠综合征（SBS）患者的液体和营养吸收。这项为期24周的安慰剂对照研究评价了替度鲁肽减少肠衰竭SBS患者肠外支持的能力。在随机接受皮下注射替度鲁肽0.10 mg/kg/天（n=32）、0.05 mg/kg/天（n=35）或安慰剂（n=16）每日一次的83例患者中，如果肠液吸收（48小时尿量）增加≥ 10%，则每隔4周减少肠外液体。 应答者为第20周和第24周时肠外容量较基线减少≥20%的受试者。主要疗效终点，分级反应评分（GRS），考虑了较高的水平和较早的反应发生，导致反应持续时间较长。反应强度定义为肠外容量较基线减少（从20%降至100%），反应持续时间视为第16、20和24周的反应。从0.10 mg/kg/天剂量开始，根据逐步下降程序检测结果。 使用GRS标准，与安慰剂相比，0.10 mg/kg/天剂量的替度鲁肽没有统计学显著性效应（8/32 vs 1/16，p=0.16），而0.05 mg/kg/天剂量的替度鲁肽具有显著性效应（16/35，p=0.007）。 由于胃肠外容量减少相等（353±475和354±334 ml/天），因此与0.05 mg/kg/天剂量组相比，0.10 mg/kg/天剂量组基线胃肠外容量（1816±1008 vs 1374±639 ml/天，p=0.11）更高的趋势可能解释了该差异。 3例接受替度格列肽治疗的患者完全脱离肠外支持。严重不良事件在活性治疗组和安慰剂组之间的分布相似。与安慰剂组相比，替度鲁肽组绒毛高度、血浆瓜氨酸浓度和瘦体重显著增加。替度鲁肽安全、耐受性良好、具有促神经营养作用，提示其具有促进吸收的作用，可减少SBS伴肠衰竭患者的肠外支持。NCT00172185。
Teduglutide, a GLP-2 analogue, may restore intestinal structural and functional integrity by promoting repair and growth of the mucosa and reducing gastric emptying and secretion, thereby increasing fluid and nutrient absorption in patients with short bowel syndrome (SBS). This 24-week placebo-controlled study evaluated the ability of teduglutide to reduce parenteral support in patients with SBS with intestinal failure. In 83 patients randomised to receive subcutaneous teduglutide 0.10 mg/kg/day (n=32), 0.05 mg/kg/day (n=35) or placebo (n=16) once daily, parenteral fluids were reduced at 4-week intervals if intestinal fluid absorption (48 h urine volumes) increased ≥10%. Responders were subjects who demonstrated reductions of ≥20% in parenteral volumes from baseline at weeks 20 and 24. The primary efficacy end point, a graded response score (GRS), took into account higher levels and earlier onset of response, leading to longer duration of response. The intensity of the response was defined as a reduction from baseline in parenteral volume (from 20% to 100%), and the duration of the response was considered the response at weeks 16, 20 and 24. The results were tested according to a step-down procedure starting with the 0.10 mg/kg/day dose. Using the GRS criteria, teduglutide in a dose of 0.10 mg/kg/day did not have a statistically significant effect compared with placebo (8/32 vs 1/16, p=0.16), while teduglutide in a dose of 0.05 mg/kg/day had a significant effect (16/35, p=0.007). Since parenteral volume reductions were equal (353±475 and 354±334 ml/day), the trend towards higher baseline parenteral volume (1816±1008 vs 1374±639 ml/day, p=0.11) in the 0.10 mg/kg/day group compared with the 0.05 mg/kg/day group may have accounted for this discrepancy. Three teduglutide-treated patients were completely weaned off parenteral support. Serious adverse events were distributed similarly between active treatment groups and placebo. Villus height, plasma citrulline concentration and lean body mass were significantly increased with teduglutide compared with placebo. Teduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure. NCT00172185.
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影响因子：
4.1
作者：
Henriksen, Dennis B.;Alexandersen, Peter;Christiansen, Claus
通讯作者：
Christiansen, Claus
影响因子：
24.5
作者：
Cani PD;Possemiers S;Van de Wiele T;Guiot Y;Everard A;Rottier O;Geurts L;Naslain D;Neyrinck A;Lambert DM;Muccioli GG;Delzenne NM
通讯作者：
Delzenne NM
影响因子：
2
作者：
Jeppesen PB;Lund P;Gottschalck IB;Nielsen HB;Holst JJ;Mortensen J;Poulsen SS;Quistorff B;Mortensen PB
通讯作者：
Mortensen PB
影响因子：
29.4
作者：
Jeppesen, PB;Hartmann, B;Mortensen, PB
通讯作者：
Mortensen, PB
影响因子：
29.4
作者：
Messing, B;Crenn, P;Matuchansky, C
通讯作者：
Matuchansky, C