Reduction by Pasireotide of the Effluent Volume in High-output Enterostomy in Patients Refractory to Usual Medical Treatment (SOMILEO)

Civil Hospices of Lyon

Status and phase: Completed; Phase 2

Conditions: Enterostomy

Treatments: Drug: Placebo; Drug: Pasireotide

Study type: Interventional

Funder types: Other

Identifiers

NCT02713776

2014_880

Details and patient eligibility

About

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.

Enrollment: 57 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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57 participants in 2 patient groups, including a placebo group

Pasireotide

Experimental group

Description:

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.

Treatment:

Drug: Pasireotide

Placebo

Placebo Comparator group

Description:

Placebo by subcutaneous injection twice a day during 3 days and 1 intramuscular injection of placebo on Day 4 morning.

Treatment:

Drug: Placebo