Clinical trial NCT02713776: Reduction by Pasireotide of the Effluent Volume in High-output Enterostomy in Patients Refractory to Usual Medical Treatment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Enterostomy
Keywords: High-Output Enterostomy
Pasireotide
Somatostatin Analogues
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2016-03-21
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Compare the efficacy of pasireotide versus placebo in reduction of high-output
timeFrame: Evaluated 72 hours after first injection of treatment
Secondary outcomes:
measure: Estimate the success rate of pasireotide and placebo
timeFrame: 1 week after first injection of treatment
measure: Compare the decrease in the length of hospitalization with pasireotide versus placebo
timeFrame: 1 month after the end of treatment
measure: Compare the incidence of premature closure of stoma due to high-output with pasireotide versus placebo
timeFrame: 2 months after enterostomy creation
measure: Evaluate the economic impact of pasireotide in this indication
timeFrame: 2 months from the inclusion of the patient in the study
measure: Incidence of treatment - Emergent Adverse Events
timeFrame: during treatment (4 days), one week, two weeks, three weeks and one month after treatment
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens-Picardie
city: Clermont-Ferrand
country: France
facility: Chu Estaing
city: Clichy
country: France
facility: Hopital Beaujon
city: La Tronche
country: France
facility: Chu Albert Michallon
city: Lille
country: France
facility: Hôpital Claude HURIEZ - CHRU Lille
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Chu Marseille - Hopital Nord
city: Montpellier
country: France
facility: Institut Regional Du Cancer Val D'Aurelle
city: Nîmes
country: France
facility: Chu Caremeau
city: Paris
country: France
facility: Hopital Saint Antoine
city: Pessac
country: France
facility: Bordeaux Chu - Hopital Haut-Leveque
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Chu Rouen Ch. Nicolle
city: Toulouse
country: France
facility: Toulouse - Chu Purpan
Study officials:
affiliation: Hospices Civils de Lyon - Centre Hospitalier Lyon Sud
name: Eddy COTTE, Professor
role: PRINCIPAL_INVESTIGATOR
References: