schliessen

Filtern

 

Bibliotheken

Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome

Background and aimsTeduglutide, 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... Full description

Journal Title: Gut 2011-07, Vol.60 (7), p.902-914
Main Author: Jeppesen, P B
Other Authors: Gilroy, R , Pertkiewicz, M , Allard, J P , Messing, B , O'Keefe, S J
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: London: BMJ Publishing Group Ltd and British Society of Gastroenterology
ID: ISSN: 0017-5749
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_istex_primary_ark_67375_NVC_30QWRN11_T
title: Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome
format: Article
creator:
  • Jeppesen, P B
  • Gilroy, R
  • Pertkiewicz, M
  • Allard, J P
  • Messing, B
  • O'Keefe, S J
subjects:
  • 1506
  • Adaptation
  • Adult
  • Aged
  • Algorithms
  • Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
  • Biological and medical sciences
  • Body Composition - drug effects
  • Body Weight - drug effects
  • Catheters
  • Combined Modality Therapy
  • Dosage and administration
  • Dose-Response Relationship, Drug
  • Drug therapy
  • Drug utilization
  • Electrolytes
  • Emergency and intensive care: metabolism and nutrition disorders. Enteral and parenteral nutrition
  • Female
  • Fluid Therapy - methods
  • Fluids
  • Gastroenterology. Liver. Pancreas. Abdomen
  • Gastrointestinal Agents - administration & dosage
  • Gastrointestinal Agents - adverse effects
  • Gastrointestinal Agents - therapeutic use
  • glucagen
  • glucagen-like peptides
  • glucagon
  • glucagon-like peptide 2
  • Humans
  • Intensive care medicine
  • intestinal failure
  • like peptide 2
  • like peptides
  • Malabsorption syndromes
  • Male
  • Medical sciences
  • Middle Aged
  • Nutrition
  • Ostomy
  • Other diseases. Semiology
  • Parenteral nutrition
  • Parenteral Nutrition - methods
  • Peptides - administration & dosage
  • Peptides - adverse effects
  • Peptides - therapeutic use
  • Placebos
  • Quality of life
  • Short bowel syndrome
  • Short Bowel Syndrome - drug therapy
  • Short Bowel Syndrome - pathology
  • Short Bowel Syndrome - physiopathology
  • Short Bowel Syndrome - therapy
  • Small Bowel
  • Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
  • Studies
  • teduglutide
  • Trace elements
  • Treatment Outcome
  • Urine
  • Weaning
  • Young Adult
ispartof: Gut, 2011-07, Vol.60 (7), p.902-914
description: Background and aimsTeduglutide, 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.MethodsIn 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.ResultsUsing 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.ConclusionsTeduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure.ClinicalTrials.gov numberNCT00172185.
language: eng
source:
identifier: ISSN: 0017-5749
fulltext: no_fulltext
issn:
  • 0017-5749
  • 1468-3288
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.7288198
LOCALfalse
PrimoNMBib
record
control
sourceidgale_opena
recordidTN_cdi_istex_primary_ark_67375_NVC_30QWRN11_T
sourceformatXML
sourcesystemPC
galeidA260651735
sourcerecordidA260651735
originalsourceidFETCH-LOGICAL-1694t-9d1cae327defbf2a118709b593462b9afa66167b8a4ffaef6757083128ad651b0
addsrcrecordideNqFktFr1TAUxosobk6ffZOCCCJ0S9I2SV8GY6gTxsQx9TGk6eldZm5yl6Sb-2v8Vz31zs0NUfrQJv19X845-YriOSXblNZ8ZzHlbUZwxahkgj4oNmnDZVUzKR8Wm4RQUbWi6TaKJymdEUKk7OjjYoPRmgoqyGbx41j7ISxtgqFcOW2gD5UJPsfgHG7laLUrw1hmGKaFm7IdoLS-jLg01i_KlY7gM0Sk_IR0tsGXaLkTInI56gvwYUrl6CY7oOx8shGWKEmzzUpn--v70ubTMp2GmMs-XIIr05UfYljC0-LRqF2CZ9fvreLzu7cn-wfV4cf3H_b3DivKuyZX3UCNhpqJAcZ-ZJpSKUjXt13dcNZ3etScUy56qZtx1DBy0Qoia8qkHnhLe7JV7K59V1O_hMHAXLtTq2iXOl6poK26-8fbU7UIF6qmlNW8QYODtUFYgdfY5B3t4CGrMCjGhZJasqYH0VAwpulM33IQuu0NH2cjg1avr2uJ4XyClBXejwHntAecpaKixbbwBhmiL--hZ2GKHieFlOjqlsiuvaUW2oGyfgzYgplN1R7jBAcg6pna_guFzwBLi5mA0eL-HcHOWmBiSCnCeNMyJWqOp8J4qjmeah1PVLz4c8o3_O88IvDqGtDJaDdG7Y1Nt1zDmGzaGrn23tHGZj2HD2u27h8FVGudTRm-3_jq-E1xUYtWHX3ZVzX59PX4iFJ1gvybNd8vz_7b3U-qlh4r
sourcetypeOpen Access Repository
isCDItrue
recordtypearticle
pqid1779350895
display
typearticle
titleRandomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome
creatorJeppesen, P B ; Gilroy, R ; Pertkiewicz, M ; Allard, J P ; Messing, B ; O'Keefe, S J
creatorcontribJeppesen, P B ; Gilroy, R ; Pertkiewicz, M ; Allard, J P ; Messing, B ; O'Keefe, S J
descriptionBackground and aimsTeduglutide, 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.MethodsIn 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.ResultsUsing 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.ConclusionsTeduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure.ClinicalTrials.gov numberNCT00172185.
identifier
0ISSN: 0017-5749
1EISSN: 1468-3288
2DOI: 10.1136/gut.2010.218271
3PMID: 21317170
4CODEN: GUTTAK
languageeng
publisherLondon: BMJ Publishing Group Ltd and British Society of Gastroenterology
subject1506 ; Adaptation ; Adult ; Aged ; Algorithms ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Biological and medical sciences ; Body Composition - drug effects ; Body Weight - drug effects ; Catheters ; Combined Modality Therapy ; Dosage and administration ; Dose-Response Relationship, Drug ; Drug therapy ; Drug utilization ; Electrolytes ; Emergency and intensive care: metabolism and nutrition disorders. Enteral and parenteral nutrition ; Female ; Fluid Therapy - methods ; Fluids ; Gastroenterology. Liver. Pancreas. Abdomen ; Gastrointestinal Agents - administration & dosage ; Gastrointestinal Agents - adverse effects ; Gastrointestinal Agents - therapeutic use ; glucagen ; glucagen-like peptides ; glucagon ; glucagon-like peptide 2 ; Humans ; Intensive care medicine ; intestinal failure ; like peptide 2 ; like peptides ; Malabsorption syndromes ; Male ; Medical sciences ; Middle Aged ; Nutrition ; Ostomy ; Other diseases. Semiology ; Parenteral nutrition ; Parenteral Nutrition - methods ; Peptides - administration & dosage ; Peptides - adverse effects ; Peptides - therapeutic use ; Placebos ; Quality of life ; Short bowel syndrome ; Short Bowel Syndrome - drug therapy ; Short Bowel Syndrome - pathology ; Short Bowel Syndrome - physiopathology ; Short Bowel Syndrome - therapy ; Small Bowel ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Studies ; teduglutide ; Trace elements ; Treatment Outcome ; Urine ; Weaning ; Young Adult
ispartofGut, 2011-07, Vol.60 (7), p.902-914
rights
02011, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
12015 INIST-CNRS
2Copyright: 2011 (c) 2011, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
32011, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. 2011
lds50peer_reviewed
oafree_for_read
citedbyFETCH-LOGICAL-1694t-9d1cae327defbf2a118709b593462b9afa66167b8a4ffaef6757083128ad651b0
links
openurl$$Topenurl_article
thumbnail$$Usyndetics_thumb_exl
backlink
0$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24228453$$DView record in Pascal Francis
1$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21317170$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0Jeppesen, P B
1Gilroy, R
2Pertkiewicz, M
3Allard, J P
4Messing, B
5O'Keefe, S J
title
0Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome
1Gut
addtitleGut
descriptionBackground and aimsTeduglutide, 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.MethodsIn 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.ResultsUsing 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.ConclusionsTeduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure.ClinicalTrials.gov numberNCT00172185.
subject
01506
1Adaptation
2Adult
3Aged
4Algorithms
5Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
6Biological and medical sciences
7Body Composition - drug effects
8Body Weight - drug effects
9Catheters
10Combined Modality Therapy
11Dosage and administration
12Dose-Response Relationship, Drug
13Drug therapy
14Drug utilization
15Electrolytes
16Emergency and intensive care: metabolism and nutrition disorders. Enteral and parenteral nutrition
17Female
18Fluid Therapy - methods
19Fluids
20Gastroenterology. Liver. Pancreas. Abdomen
21Gastrointestinal Agents - administration & dosage
22Gastrointestinal Agents - adverse effects
23Gastrointestinal Agents - therapeutic use
24glucagen
25glucagen-like peptides
26glucagon
27glucagon-like peptide 2
28Humans
29Intensive care medicine
30intestinal failure
31like peptide 2
32like peptides
33Malabsorption syndromes
34Male
35Medical sciences
36Middle Aged
37Nutrition
38Ostomy
39Other diseases. Semiology
40Parenteral nutrition
41Parenteral Nutrition - methods
42Peptides - administration & dosage
43Peptides - adverse effects
44Peptides - therapeutic use
45Placebos
46Quality of life
47Short bowel syndrome
48Short Bowel Syndrome - drug therapy
49Short Bowel Syndrome - pathology
50Short Bowel Syndrome - physiopathology
51Short Bowel Syndrome - therapy
52Small Bowel
53Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
54Studies
55teduglutide
56Trace elements
57Treatment Outcome
58Urine
59Weaning
60Young Adult
issn
00017-5749
11468-3288
fulltextfalse
rsrctypearticle
creationdate2011
recordtypearticle
recordideNqFktFr1TAUxosobk6ffZOCCCJ0S9I2SV8GY6gTxsQx9TGk6eldZm5yl6Sb-2v8Vz31zs0NUfrQJv19X845-YriOSXblNZ8ZzHlbUZwxahkgj4oNmnDZVUzKR8Wm4RQUbWi6TaKJymdEUKk7OjjYoPRmgoqyGbx41j7ISxtgqFcOW2gD5UJPsfgHG7laLUrw1hmGKaFm7IdoLS-jLg01i_KlY7gM0Sk_IR0tsGXaLkTInI56gvwYUrl6CY7oOx8shGWKEmzzUpn--v70ubTMp2GmMs-XIIr05UfYljC0-LRqF2CZ9fvreLzu7cn-wfV4cf3H_b3DivKuyZX3UCNhpqJAcZ-ZJpSKUjXt13dcNZ3etScUy56qZtx1DBy0Qoia8qkHnhLe7JV7K59V1O_hMHAXLtTq2iXOl6poK26-8fbU7UIF6qmlNW8QYODtUFYgdfY5B3t4CGrMCjGhZJasqYH0VAwpulM33IQuu0NH2cjg1avr2uJ4XyClBXejwHntAecpaKixbbwBhmiL--hZ2GKHieFlOjqlsiuvaUW2oGyfgzYgplN1R7jBAcg6pna_guFzwBLi5mA0eL-HcHOWmBiSCnCeNMyJWqOp8J4qjmeah1PVLz4c8o3_O88IvDqGtDJaDdG7Y1Nt1zDmGzaGrn23tHGZj2HD2u27h8FVGudTRm-3_jq-E1xUYtWHX3ZVzX59PX4iFJ1gvybNd8vz_7b3U-qlh4r
startdate201107
enddate201107
creator
0Jeppesen, P B
1Gilroy, R
2Pertkiewicz, M
3Allard, J P
4Messing, B
5O'Keefe, S J
general
0BMJ Publishing Group Ltd and British Society of Gastroenterology
1BMJ Publishing Group
2BMJ Publishing Group Ltd
3BMJ Publishing Group LTD
4BMJ Group
scope
0BSCLL
1IQODW
2CGR
3CUY
4CVF
5ECM
6EIF
7NPM
8AAYXX
9CITATION
10BSHEE
113V.
127X7
137XB
1488E
1588I
168AF
178FE
188FH
198FI
208FJ
218FK
22ABUWG
23AZQEC
24BBNVY
25BENPR
26BHPHI
27BTHHO
28DWQXO
29FYUFA
30GHDGH
31GNUQQ
32HCIFZ
33K9.
34LK8
35M0S
36M1P
37M2P
38M7P
39PQEST
40PQQKQ
41PQUKI
42PRINS
43Q9U
447T5
45H94
46BOBZL
47CLFQK
485PM
sort
creationdate201107
titleRandomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome
authorJeppesen, P B ; Gilroy, R ; Pertkiewicz, M ; Allard, J P ; Messing, B ; O'Keefe, S J
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1694t-9d1cae327defbf2a118709b593462b9afa66167b8a4ffaef6757083128ad651b0
rsrctypearticles
prefilterarticles
languageeng
creationdate2011
topic
01506
1Adaptation
2Adult
3Aged
4Algorithms
5Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
6Biological and medical sciences
7Body Composition - drug effects
8Body Weight - drug effects
9Catheters
10Combined Modality Therapy
11Dosage and administration
12Dose-Response Relationship, Drug
13Drug therapy
14Drug utilization
15Electrolytes
16Emergency and intensive care: metabolism and nutrition disorders. Enteral and parenteral nutrition
17Female
18Fluid Therapy - methods
19Fluids
20Gastroenterology. Liver. Pancreas. Abdomen
21Gastrointestinal Agents - administration & dosage
22Gastrointestinal Agents - adverse effects
23Gastrointestinal Agents - therapeutic use
24glucagen
25glucagen-like peptides
26glucagon
27glucagon-like peptide 2
28Humans
29Intensive care medicine
30intestinal failure
31like peptide 2
32like peptides
33Malabsorption syndromes
34Male
35Medical sciences
36Middle Aged
37Nutrition
38Ostomy
39Other diseases. Semiology
40Parenteral nutrition
41Parenteral Nutrition - methods
42Peptides - administration & dosage
43Peptides - adverse effects
44Peptides - therapeutic use
45Placebos
46Quality of life
47Short bowel syndrome
48Short Bowel Syndrome - drug therapy
49Short Bowel Syndrome - pathology
50Short Bowel Syndrome - physiopathology
51Short Bowel Syndrome - therapy
52Small Bowel
53Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
54Studies
55teduglutide
56Trace elements
57Treatment Outcome
58Urine
59Weaning
60Young Adult
toplevelpeer_reviewed
creatorcontrib
0Jeppesen, P B
1Gilroy, R
2Pertkiewicz, M
3Allard, J P
4Messing, B
5O'Keefe, S J
collection
0Istex
1Pascal-Francis
2Medline
3MEDLINE
4MEDLINE (Ovid)
5MEDLINE
6MEDLINE
7PubMed
8CrossRef
9Academic OneFile (A&I only)
10ProQuest Central (Corporate)
11Health & Medical Collection
12ProQuest Central (purchase pre-March 2016)
13Medical Database (Alumni Edition)
14Science Database (Alumni Edition)
15STEM Database
16ProQuest SciTech Collection
17ProQuest Natural Science Collection
18Hospital Premium Collection
19Hospital Premium Collection (Alumni Edition)
20ProQuest Central (Alumni) (purchase pre-March 2016)
21ProQuest Central (Alumni Edition)
22ProQuest Central Essentials
23Biological Science Collection
24ProQuest Central
25Natural Science Collection
26BMJ Journals
27ProQuest Central Korea
28Health Research Premium Collection
29Health Research Premium Collection (Alumni)
30ProQuest Central Student
31SciTech Premium Collection
32ProQuest Health & Medical Complete (Alumni)
33ProQuest Biological Science Collection
34Health & Medical Collection (Alumni Edition)
35Medical Database
36Science Database
37Biological Science Database
38ProQuest One Academic Eastern Edition
39ProQuest One Academic
40ProQuest One Academic UKI Edition
41ProQuest Central China
42ProQuest Central Basic
43Immunology Abstracts
44AIDS and Cancer Research Abstracts
45OpenAIRE (Open Access)
46OpenAIRE
47PubMed Central (Full Participant titles)
jtitleGut
delivery
delcategoryRemote Search Resource
fulltextno_fulltext
addata
au
0Jeppesen, P B
1Gilroy, R
2Pertkiewicz, M
3Allard, J P
4Messing, B
5O'Keefe, S J
formatjournal
genrearticle
ristypeJOUR
atitleRandomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome
jtitleGut
addtitleGut
date2011-07
risdate2011
volume60
issue7
spage902
epage914
pages902-914
issn0017-5749
eissn1468-3288
codenGUTTAK
abstractBackground and aimsTeduglutide, 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.MethodsIn 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.ResultsUsing 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.ConclusionsTeduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure.ClinicalTrials.gov numberNCT00172185.
copLondon
pubBMJ Publishing Group Ltd and British Society of Gastroenterology
pmid21317170
doi10.1136/gut.2010.218271
oafree_for_read