Reduction by Pasireotide of the Effluent Volume in High-output Enterostomy in Patients Refractory to Usual Medical Treatment : Phase II Multicentric Randomized Double Bland Placebo Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 14
- 主要终点
- Compare the efficacy of pasireotide versus placebo in reduction of high-output
研究概览
简要总结
During rectal or complex digestive surgery with multiple digestive resections and anastomosis, the creation of enterostomy is a common procedure. In France, it is estimated that 20000 patients have an ileostomy and 16000 new digestive stomas are formed each year with approximately 30% of enterostomy. Enterostomy might sometimes give high-output not controlled with usual medical treatment (e.g loperamide ± codeine) and exposes the patients to important hydro-electrolytic loss leading to a risk for dehydration, electrolyte abnormalities and acute renal failure. This risk implies parenteral correction which may extend hospital stay and delay home return.
Somatostatin analogues (octreotide, lanreotide and pasireotide) could reduce digestive secretions and decrease digestive peristalsis. Nevertheless, somatostatin analogues are not routinely used for the treatment of patients with high-output enterostomy and their efficacy in the indication (off-label) was only tested in small case series. Pasireotide (SOM230, SIGNIFOR®) is currently indicated for the treatment of patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed.
As the efficacity of pasireotide in patients with high-output enterostomy refractory to usual medical treatment associated with an oral fluid restriction has never been demonstrated before, there is a need to perform a pilot, double-blind, randomized, placebo-controlled trial evaluating its impact on reduction of the effluent volume.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and Female patients ≥ 18 years old ;
- •Patients who underwent an intestinal surgery with enterostomy repair in the three weeks preceding the inclusion ;
- •Patients with high-output ileostomy or jejunostomy > 1000 ml/24h ;
- •Patients with failure of treatment combining oral fluid restriction and loperamide (up to 8 capsules/24h) +/- codeine syrup (10 mg x 3/24h) during 5 days ;
- •Patients who gave its written informed consent to participate to the study ;
- •Patients affiliated to a social insurance regime.
排除标准
- •Male and Female patients < 18 years old ;
- •Patients who did not give its written informed consent to participate to the study ;
- •Patients who received somatostatin analogues during the month before inclusion ;
- •Patients with symptomatic cholelithiasis or acute or chronic pancreatitis ;
- •Patients with uncontrolled diabetes (with HbA1c (glycated hemoglobin) > 8%) ;
- •Patients who are hypothyroid and not on adequate replacement therapy ;
- •Patients who have congestive heart failure (NYHA (New York Heart Association) Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, advanced heart block or a history of clinically significant bradycardia or acute myocardial infarction within the 6 months preceding randomization ;
- •Patients with history of syncope or family history of idiopathic sudden death ;
- •Patients with screening or baseline (predose) : QT interval corrected for heart rate using Fridericia's correction (QTcF) QTcF > 450 msec (male), QTcF > 460 msec (female) (QT interval corrected for heart rate using Fridericia's correction) ;
- •Patients with not corrected hypokalaemia and/or hypomagnesaemia ;
- •Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with alanine transaminase/aspartate transaminase (ALT/AST) > 2 x Upper Limit of Normal (ULN), serum bilirubin > 2 x ULN ;
- •Patients with Child-Pugh C cirrhosis ;
- •Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control ;
- •Patients with abnormal coagulation (PT and/or APTT elevated by 30% above normal limits) or patients receiving anticoagulants that affect PT (prothrombin time) or activated partial thromboplastin time (APTT) ;
- •Patients with known hypersensitivity to somatostatin analogues or any other component of the pasireotide LAR ;
- •Patients under guardianship ;
- •Patients nonaffiliated to a social insurance regime.
研究组 & 干预措施
Pasireotide
Pasireotide 0.9 mg by subcutaneous injection twice a day during 3 days and 1 intramuscular injection of pasireotide Long Acting Release (LAR) 60mg on Day 4 morning.
干预措施: Pasireotide (Drug)
Placebo
Placebo by subcutaneous injection twice a day during 3 days and 1 intramuscular injection of placebo on Day 4 morning.
干预措施: Placebo (Drug)
结局指标
主要结局
Compare the efficacy of pasireotide versus placebo in reduction of high-output
时间窗: Evaluated 72 hours after first injection of treatment
Decrease of enterostomy output (ml/24H)within the 72 hours after first injection of treatment
次要结局
- Estimate the success rate of pasireotide and placebo(1 week after first injection of treatment)
- Incidence of treatment - Emergent Adverse Events(during treatment (4 days), one week, two weeks, three weeks and one month after treatment)
- Compare the decrease in the length of hospitalization with pasireotide versus placebo(1 month after the end of treatment)
- Compare the incidence of premature closure of stoma due to high-output with pasireotide versus placebo(2 months after enterostomy creation)
- Evaluate the economic impact of pasireotide in this indication(2 months from the inclusion of the patient in the study)