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The Cochrane Database of Systematic Reviews logoLink to The Cochrane Database of Systematic Reviews
. 2021 Jul 30;2021(7):CD014216. doi: 10.1002/14651858.CD014216

Teduglutide for the treatment of patients with short bowel syndrome

Maria C Riutort 1, Gigliola Alberti 1,✉, Juan Cristóbal Gana 2, Luis A Villarroel del Pino 3, Lorena I Cifuentes 4, Marcela Rivera-Cornejo 5
Editor: Cochrane Gut Group
PMCID: PMC8406819

Objectives

This is a protocol for a Cochrane Review (intervention). The objectives are as follows:

To evaluate the safety and efficacy of teduglutide for the treatment of patients with short bowel syndrome when compared with placebo or no intervention.

Background

Short bowel syndrome (SBS) is a disease that occurs secondary to the loss of the intestinal absorption capacity that may lead to diarrhea, fatty stools, dehydration, electrolyte disturbances, malabsorption and malnutrition (Kelly 2014; Tappenden 2014; Uko 2012). SBS happens after a resection of a large segment of the small bowel, either by congenital or acquired lesions and secondary dysmotility and malabsorption/maldigestion, resulting in a loss of the absorption area (Diamanti 2021; O'Keefe 2006). While on a normal diet, SBS fails to maintain balance in macronutrients, micronutrients and fluids (O'Keefe 2006). In children, it results in the inability to maintain proper growth and development (Goulet 2004; Youssef 2012).

Patients with SBS usually require a prolonged nutritional support. The use of chronic parenteral nutrition (> 90 days) is associated with adverse effects, such as mechanical complications due to the use of a central venous catheter, bloodstream infections and parenteral nutrition‐associated liver disease, that usually manifests as cholestasis, steatosis, cholelitiasis, liver fibrosis and cirrhosis (Duro 2008; O'Keefe 2006; Vipperla 2011; Xu 2012). Furthermore, patients with chronic parenteral nutrition have impaired quality of life (Carlsson 2003; Hukkinen 2018; Jeppesen 1999; Winkler 2005; Winkler 2014) and impairments in motor and mental skills (Hukkinen 2018). These complications represent the main causes of mortality in patients with SBS (Schalamon 2003; Wales 2004; Wales 2005).

The goal of medical therapy is to achieve a normal lifestyle, by decreasing the requirements of parenteral nutrition and avoiding its complications. The main goals of medical management are to provide adequate nutrition and sufficient fluids, and to correct and prevent acid‐base disturbances (Buchman 2003).

Description of the condition

SBS is a spectrum of malabsorption that occurs as a consequence of a resection of a large portion of small bowel, either by a congenital or acquired lesion (Kelly 2014). Patients with SBS have a spectrum of bowel dysfunction, ranging from compensated intestinal insufficiency to intestinal failure (Jeppesen 2014; O'Keefe 2006; Schwartz 2016). The prevalence of this condition is unknown (Jeppesen 2014).

Intestinal adaptation is a process that follows the resection of the small bowel and aims to restore the normal absorption of macronutrient, water and minerals (DiBaise 2004; Goodlad 2001; Jeppesen 2006; Seidner 2013). It depends on different factors, including the cause of the condition, the length and the anatomy of the remaining segment, the presence or absence of the colon, the age of the patient, the presence of comorbidities, presence of food intake and non‐nutrient endogenous peptide factors (Buchman 2003; Vipperla 2011). The process of adaptation implicates both structural and functional changes that improve the proper functioning of the remaining intestinal segment (Kelly 2014). The structural component includes augmentation of the absorptive area of the remnant intestine that includes gain in the crypt depth, increase in villus height, cellular hyperplasia, increase in the bowel diameter and enhanced mucosal proliferation (Buchman 2003; Doldi 1991; Kelly 2014; Tappenden 2014). The functional component is characterized mainly by slowing the rate of gastrointestinal transit and allowing increased time for absorption (Brown 2004; Tappenden 2014). This adaptive process begins early, within the first 12 to 24 hours following the intestinal resection, and can be ongoing for several months or even years (Buchman 2003; O'Keefe 2006). Nutritional support has an important role in adaptation (Olieman 2020). Predictors of intestinal adaptation in children include greater length of the remnant small bowel, preservation of the ileocecal valve and of the colon, the continuity of the intestine, necrotizing enterocolitis, type of enteral nutrition, absence of complications, and the care received (multidisciplinary intestinal rehabilitation programs) (Tannuri 2016; Venick 2019). 

Description of the intervention

Different medical strategies to diminish the consequences of chronic parenteral nutrition and to enhance the intestinal adaptation process have been developed (Kocoshis 2010; Martin 2006; Seidner 2013; Tappenden 2014). Among these, the use of growth hormone and glutamine (Uko 2012) have been proposed. A systematic review in adult patients with SBS evaluated the efficacy of growth hormone alone, and growth hormone with glutamine supplementation. Despite the positive effect in weight gain and energy absorption, this response was transient (Wales 2010).

Another trophic factor studied is the glucagon‐like peptide‐2 (GLP‐2), a neuroendocrine peptide which is usually produced by the L cells (that are situated in the terminal ileum and colon), in response to luminal nutrients, especially long‐chain free fatty acids and carbohydrates (Jeppesen 2005; Sigalet 2018). It has been related to intestinal adaptation through induction of the proliferation of crypt cells in the colon and the prevention of enterocyte apoptosis (Uko 2012). GLP‐2 is produced in infants, with higher serum GLP‐2 concentrations in patients with small bowel‐colic continuity (Mutanen 2017).

Within the functions of GLP‐2 are the reduction of the gastric acid secretion, the inhibition of gastric antral emptying, the stimulation of intestinal blood flow, the enhancement of the intestinal barrier function, the augmented intestinal transit time, the improvement in bone mineral density and the stimulation of nutrients and fluids absorption (Drucker 2002; Jeppesen 2013; Vipperla 2011). Acutely, GLP‐2 slows motility, increases mesenteric blood flow and reduces enteric secretions. Chronically, it is a trophic factor for the small bowel mucosa (Sigalet 2018).

Teduglutide is a recombinant analogue of the human GLP‐2 that differs in the substitution of amino acids (alanine by glycine) at the second position at the N‐terminus, giving it the property of being resistant to in vivo degradation. This gives a longer half life than GLP‐2 (Youssef 2012), allowing its administration once a day by subcutaneous injection (Burness 2013; Peterson 2012). It is the first long‐term therapy approved for the treatment of patients with SBS that are dependent on parenteral nutrition.

How the intervention might work

Teduglutide is able to modulate intestinal adaptation, to promote fluid and nutrient absorption and to increase intestinal growth (Jeppesen 2013). It has been proved that teduglutide improves various parameters, as it reduces fecal wet weight and fecal energy excretion, increases urinary output, and improves nutrient and energy absorption (Burness 2013; Jeppesen 2005; Jeppesen 2012; Seidner 2013; Sigalet 2018; Vipperla 2011). Teduglutide also improves lean body mass and total body bone mineral content (Jeppesen 2011), increases plasma levels of citrulline (reflects the residual functional intestinal mass) in patients with SBS, and reduces parenteral nutrition requirements (Jeppesen 2012; Sigalet 2018).

Why it is important to do this review

Patients with SBS must have a multidisciplinary approach, oriented towards promoting intestinal adaptation and recovery of the function of the intestine in order to reach intestinal autonomy. To achieve these objectives, it is important to have tools that allow us to improve the process of intestinal adaptation and achieve reduction or independence on parenteral nutrition requirements. The aim of effective medical therapies is to decrease the use of parenteral nutrition. This could prevent some of the major complications associated with its use, thus decreasing the morbidity and mortality of patients. This may lead to a decline in the number of hospitalizations for infections associated with the use of a central venous catheter, which could also contribute to reducing the numbers of patients requiring liver transplant as a consequence of the development of hepatic disease associated with parenteral nutrition.

Objectives

To evaluate the safety and efficacy of teduglutide for the treatment of patients with short bowel syndrome when compared with placebo or no intervention.

Methods

Criteria for considering studies for this review

Types of studies

Randomized controlled trials (RCT) will be included. We will also include cluster and cross‐over trials.

Types of participants

Patients with short bowel syndrome, regardless of the cause, dependent on parenteral nutrition or intravenous fluids. There will be no limit on age.

Types of interventions

RCTs comparing teduglutide with placebo or no intervention.

Types of outcome measures

We will collect data with a range of follow‐up and will also assess all outcomes at the longest follow‐up.

Primary outcomes

1. Decrease in the requirements of parenteral nutrition or parenteral fluids: decrease in number of days per week of PN or parenteral fluids, or decrease of volume of PN or parenteral fluids per kg body weight (change score).

2. Serious adverse events: catheter‐related complications, small bowel obstruction, sepsis, fever, biliary or pancreatic disease, malignancy. According to the International Conference on Harmonisation (ICH) Guidelines for Good Clinical Practice (ICH‐GCP 1997), a serious adverse event is any untoward medical occurrence that: results in death; is life‐threatening; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability or incapacity; or is a congenital anomaly or birth defect. All other adverse events were considered non‐serious adverse events.

Secondary outcomes

1. All‐cause mortality.

2. Quality of life: determined exclusively by means of validated scales, classifications and measurement systems like the Paediatric Quality of Life Inventory (PedsQL), Child Health Questionnaire (CHQ), and DISABKIDS Questionnaire.

3. Adverse effects: abdominal pain, nausea, abdominal distention, stoma complications, electrolyte disturbances (any adverse events that do not meet the above criteria for serious adverse events).

4. BMI/weight changes, lean body mass (LBM) changes.

5. Change in total energy absorption (in Kcal), and in fat, carbohydrate and nitrogen absorption.

6. Change in serum level of insulin‐like growth factor‐1 (IGF‐1) (ng/mL).

We plan to collect follow‐up data for the listed outcomes during the trial period, and up to five years follow‐up.  

Search methods for identification of studies

Electronic searches

We will design the search strategies with the help of the Cochrane Gut Information Specialist before performing literature searches. We will conduct the searches in the following sources:

  • Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Library (until search date);

  • ClinicalTrial.gov (until search date);

  • Embase via Ovid SP (1974 ‐ search date);

  • MEDLINE via Ovid SP (1946 ‐ search date);

  • Science Citation Index Expanded via Web of science (1900 ‐ search date);

  • World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP) (until search date).

No restrictions on the language, date, document type, or publication status will be applied when searching the electronic databases or reviewing reference lists in identified studies. The search strategies are listed in Appendix 1.

Searching other resources

We will manually search the references of studies in databases or of relevant reviews for additional references. In the case of unpublished studies, we will include them only if they provide relevant data. 

Data collection and analysis

We will be following the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions for data collection and analysis (Higgins 2021). The analyses of the collected data will be done with RevMan Web (RevMan Web 2020).

Selection of studies

If a study is potentially eligible, on the basis of an abstract review, the publication will be retrieved. These studies will be evaluated independently by MCR and GA, to assess their eligibility. Each study will be examined to establish whether patients meet the previously detailed inclusion criteria. Study summaries will be incorporated only if they provide enough data for analysis. Disagreements will be solved between the authors MCR, GA and JCG by consensus.

Data extraction and management

The data of all the included studies will be managed independently by MCR and GA, with data extraction forms. Inclusion criteria are patients with short bowel syndrome, regardless of the cause, dependent on parenteral nutrition or intravenous fluids. We will exclude patients with short bowel syndrome that are weaned off of parenteral nutrition, or patients on parenteral nutrition or intravenous fluids that do not have short bowel syndrome.

With data extraction forms, we will obtain:

1. Study information: title, year of publication, journal, and publication status.

2. Characteristics of the study: study design, sample size and type of intervention.

3. Baseline characteristics of the participants: baseline diagnosis (cause of SBS), age, sex, race, BMI, remnant colon, remnant small intestine length, time on parenteral support, prescribed PN volume at study entry, parenteral energy, concomitant medications.

4. Reduction in parenteral nutrition requirements, reduction in parenteral fluids requirements, changes in weight.

5. Adverse events.

Assessment of risk of bias in included studies

Two authors (MCR and GA) will independently asses the risk of bias in included studies using version 2 of the Cochrane risk of bias tool for randomized trials (RoB 2) (Higgins 2011; RevMan Web 2020), according to the recommendations in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and methodological studies  (Kjaergard 2001; Moher 1998; Savović 2012a; Savović 2012b; Savović 2018; Schulz 1995; Wood 2008). We will use the following definitions in the assessment of risk of bias:

Allocation sequence generation

‐ Low risk of bias: sequence generation was achieved using computer random number generation or a random number table. Drawing lots, tossing a coin, shuffling cards, and throwing dice were adequate if performed by an independent person not otherwise involved in the trial.

‐ Unclear risk of bias: the method of sequence generation was not specified.

‐ High risk of bias: the sequence generation method was not random.

Allocation concealment

‐ Low risk of bias: the participant allocations could not have been foreseen in advance of, or during, enrolment. Allocation was controlled by a central and independent randomisation unit. The allocation sequence was unknown to the investigators (e.g. if the allocation sequence was hidden in sequentially numbered, opaque, and sealed envelopes).

‐ Unclear risk of bias: the method used to conceal the allocation was not described so that intervention allocations may have been foreseen in advance of, or during, enrolment.

‐ High risk of bias: the allocation sequence was likely to be known to the investigators who assigned the participants.

Blinding of participants and personnel

‐ Low risk of bias: blinding of participants and personnel performed adequately using a placebo. We will define lack of blinding as not likely to affect the evaluation of mortality (Savović 2012a; Savović 2012b).

‐ Unclear risk of bias: insufficient information to assess blinding. 

‐ High risk of bias: no blinding or incomplete blinding.

Blinding of outcome assessors

‐ Low risk of bias: blinding of outcome assessors performed adequately using a placebo. We defined lack of blinding as not likely to affect the evaluation of mortality (Savović 2012a; Savović 2012b).

‐ Unclear risk of bias: insufficient information to assess blinding.

‐ High risk of bias: no blinding or incomplete blinding.

Incomplete outcome data

‐ Low risk of bias: missing data were unlikely to make treatment effects depart from plausible values. Sufficient methods, such as multiple imputation, were employed to handle missing data.

‐ Unclear risk of bias: there was insufficient information to assess whether missing data in combination with the method used to handle missing data were likely to induce bias on the results.

‐ High risk of bias: the results were likely to be biased due to missing data.

Selective outcome reporting

‐ Low risk: the trial reported the following predefined primary outcomes: 'all‐cause mortality' and 'serious adverse events'. If the original trial protocol was available, the outcomes should be those called for in that protocol. If the trial protocol was obtained from a trial registry (e.g. www.clinicaltrials.gov), the outcomes sought were those enumerated in the original protocol if the trial protocol was registered before or at the time that the trial was begun. If the trial protocol was registered after the trial commenced, those outcomes were not considered to be reliable.

‐ Unclear risk: not all predefined outcomes were reported fully, or it was unclear whether data on these outcomes were recorded or not.

‐ High risk: one or more predefined outcomes were not reported. 

Other bias

‐ Low risk of bias: the trial appeared to be free of other bias domains including vested interests that could put it at risk of bias.

‐ Unclear risk of bias: the trial may or may not have been free of other domains that could put it at risk of bias.

‐ High risk of bias: there were other factors in the trial that could put it at risk of bias.

Overall bias risk assessment

‐ Low risk of bias: all domains in a trial were at low risk of bias using the definitions described above.

‐ High risk of bias: one or more of the bias domains in a trial were at unclear or high risk of bias.

Measures of treatment effect

For the dichotomous outcomes, relative risks (RRs) with 95% confidence intervals (95% CIs) will be used. We will calculate mean differences (MDs) with corresponding 95% CIs for continuous outcomes. For studies using various scales to measure continuous outcomes, we intend to utilize standardised mean differences (SMDs).

Unit of analysis issues

The unit of analysis will be the participant undergoing treatment according to the intervention group to which the participant was randomly assigned. In case of trials with multiple intervention groups, we plan to collect data for all trial intervention groups that meet our inclusion criteria. We plan to divide the control group into two to avoid double‐counting in case this was a common comparator. In the case of cross‐over trials, we plan to use the outcome data after the period of the first intervention because the assigned treatments could have residual effects (Higgins 2011). 

Dealing with missing data

We plan to perform an intention‐to‐treat analysis whenever possible; otherwise, we plan to analyse only the available data and to contact the original investigators to ask for the missing data. We plan to also address the potential impact of missing data on the findings using intention‐to‐treat analyses.

Regarding the dichotomous primary outcomes, whenever possible, we plan to include participants with incomplete or missing data in sensitivity analyses, by imputing data according to the following scenarios:

‐ Extreme‐case analysis favouring the experimental intervention ('best‐worse' case scenario): none of the dropouts or participants lost from the experimental arm, but all of the dropouts and participants lost from the control group experienced the outcome; including all randomized participants in the denominator.

‐ Extreme‐case analysis favouring the control ('worst‐best' case scenario): all dropouts or participants lost from the experimental arm, but none from the control arm experienced the outcome; including all randomized participants in the denominator.

For the continuous outcomes, we plan to impute the standard deviation from P values, according to guidance in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011; Higgins 2021). If the data are likely to be normally distributed, we plan to use the median for meta‐analysis when the mean is not available; otherwise, we plan to provide a median and interquartile range of the difference in medians. If it is not possible to calculate the standard deviation from the P value or the CIs, we plan to impute the standard deviation using the largest standard deviation in other trials for that outcome. This form of imputation can decrease the weight of the study for calculation of MDs and may bias the effect estimate to no effect for calculation of SMDs (Higgins 2011; Higgins 2021).

Assessment of heterogeneity

We plan to identify heterogeneity by visual inspection of the forest plots, by using a standard Chi2 test and a significance level of α = 0.1, in view of the low power of such tests. We plan to use the chi‐squared test for heterogeneity to detect between‐trial heterogeneity. In addition, we plan to specifically examine the degree of heterogeneity observed in the results with the I2 statistic according to the following classification: from 0% to 40%, heterogeneity may not be important; from 30% to 60%, heterogeneity may be moderate; from 50% to 90%, heterogeneity may be substantial; and from 75% to 100%, heterogeneity may be considerable (Higgins 2003). If heterogeneity is found, we plan to determine the potential reasons for it by examining the individual trial and subgroup characteristics.

Assessment of reporting biases

If there are 10 or more studies included in a meta‐analysis, we will construct a funnel plot to assess for potential publication bias.

Data synthesis

RevMan Web (RevMan Web 2020) will be utilized for the analyses. We plan to present results with a random‐effects meta‐analysis because we expect that the included trials will be heterogeneous. We plan to present the results of continuous outcomes as MDs or SMDs, both with 95% CIs. We plan to perform a meta‐regression to examine heterogeneity.

Subgroup analysis and investigation of heterogeneity

We intend to carry out subgroup analyses. Consequently, we will do different meta‐analyses for the studies depending on their risk of bias, adults versus children, according to the length of the remnant intestine and time receiving teduglutide (months). We will explore sources of heterogeneity including dependence on parenteral nutrition, different etiologies of SBS, comorbidities, and dose of teduglutide.

Sensitivity analysis

To evaluate the strength of the eligibility criteria, sensitivity analyses will be done. This will show which studies are causing the largest deviations from our findings, as well as to observing heterogeneity.

Summary of findings and assessment of the certainty of the evidence

We will create a summary of findings table, using GRADEpro (GRADEpro GDT) to provide information about the certainty of the evidence, the magnitude of effects of the interventions, and to summarise results on all outcomes. 

The GRADE approach appraises the certainty of a body of evidence based on the extent to which one can be confident that an estimate of effect or association reflects the item being assessed. The certainty of a body of evidence considers: within‐study risk of bias; indirectness of the evidence (population, intervention, control, outcomes); unexplained inconsistency (heterogeneity) of results (including problems with subgroup analyses); imprecision of results; and risk of publication bias.

We will classify the levels of evidence as 'high', 'moderate', 'low', or 'very low'. These grades are defined as follows:

• High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.

• Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

• Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.

• Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Acknowledgements

The authors would like to thank Professor Morris Gordon (Coordinating Editor/Sign‐off Editor), Professor Anthony Akobeng (Coordinating Editor/Contact editor), and Ghazaleh Aali (Managing Editor) at Cochrane Gut Group's UK editorial team in the University of central Lancashire for their support in completing this review.

The authors also would like to thank Dr Farhad Shokraneh for peer‐reviewing and revising the search methods and strategies.

The authors would like to thank the following editors and peer referees who provided feedback to improve the protocol: Professor Derek P Jewell, Professor Ezra Steiger, Dr Yuhong Yuan, Teo Aw Quay, Yasamin Farbod, and also the previous ‘Cochrane IBD’ editorial team.

The authors would like to thank Romina Torres‐Robles and Maria Teresa Olivares for their contribution to the protocol.

The authors also would like to thank Anne Lethaby (Copy Editor) and the Wiley Copy Editor team for providing copy editing comments.

 

Appendices

Appendix 1. Search strategy

CENTRAL via Cochrane Library

([mh "Glucagon‐Like Peptide 2"] OR GLP?2 OR Teduglutid* OR (Glucagon?Like NEXT Peptide?2) OR Gattex OR Revestive OR ALX?0600) AND ([mh "Short Bowel Syndrome"] OR ((Short Intestin* OR Short Bowel OR Short Gut) NEXT Syndrome*) OR (Resection NEAR/1 (Intestin* OR Bowel)) OR SBS)

in Trials

ClinicalTrials.gov

Advanced Search

Condition or disease: Short Bowel Syndrome OR Short Gut Syndrome

Study type: Interventional Studies (Clinical Trials)

Intervention/treatment: Teduglutide

Embase via Ovid SP

1 Glucagon Like Peptide 2/ or Teduglutide/ or (Teduglutid* or GLP?2 or (Glucagon?Like adj Peptide?2) or Gattex or Revestive or ALX?0600).mp.

2 Short Bowel Syndrome/ or (((Short Intestin* or Short Bowel or Short Gut) adj Syndrome*) or SBS or (Resection and (Bowel or Intestin*))).mp.

3 Randomized controlled trial/ or Controlled clinical study/ or randomization/ or intermethod comparison/ or double blind procedure/ or human experiment/ or (random$ or placebo or (open adj label) or ((double or single or doubly or singly) adj (blind or blinded or blindly)) or parallel group$1 or crossover or cross over or ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)) or assigned or allocated or (controlled adj7 (study or design or trial)) or volunteer or volunteers).ti,ab. or (compare or compared or comparison or trial).ti. or ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab.

4 ((random$ adj sampl$ adj7 ("cross section$" or questionnaire$1 or survey$ or database$1)).ti,ab.) not (comparative study/ or controlled study/ or randomi?ed controlled.ti,ab. or randomly assigned.ti,ab.)

5 Cross‐sectional study/ not (randomized controlled trial/ or controlled clinical study/ or controlled study/ or (randomi?ed controlled or control group$1).ti,ab.)

6 (((case adj control$) and random$) not randomi?ed controlled).ti,ab.

7 (Systematic review not (trial or study)).ti.

8 (nonrandom$ not random$).ti,ab.

9 ("Random field$" or (random cluster adj3 sampl$)).ti,ab.

10 (review.ab. and review.pt.) not trial.ti.

11 "we searched".ab. and (review.ti. or review.pt.)

12 ("update review" or (databases adj4 searched)).ab.

13 (rat or rats or mouse or mice or swine or porcine or murine or sheep or lambs or pigs or piglets or rabbit or rabbits or cat or cats or dog or dogs or cattle or bovine or monkey or monkeys or trout or marmoset$1).ti. and animal experiment/

14 Animal experiment/ not (human experiment/ or human/)

15 or/4‐14

16 3 not 15

17 1 and 2 and 16

MEDLINE via Ovid SP

1 Glucagon‐Like Peptide 2/ or (Teduglutid* or GLP?2 or (Glucagon?Like adj Peptide?2) or Gattex or Revestive or ALX?0600).mp.

2 Short Bowel Syndrome/ or (((Short Intestin* or Short Bowel or Short Gut) adj Syndrome*) or SBS or (Resection and (Bowel or Intestin*))).mp.

3 ((Randomized Controlled Trial or Controlled Clinical Trial).pt. or (Randomi?ed or Placebo or Randomly or Trial or Groups).ab. or Drug Therapy.fs.) not (exp Animals/ not Humans.sh.)

4 and/1‐3

Science Citation Index Expanded via Web of Science

Advanced Search

#4 #3 AND #2 AND #1 Indexes=SCI‐EXPANDED Timespan=All years

#3 TI=(Random* OR Placebo OR Blind* OR Trial OR Groups) OR AB=(Random* OR Placebo OR Blind* OR Trial OR Groups) Indexes=SCI‐EXPANDED Timespan=All years

#2 TI=(Short Bowel OR Small Intestine OR Short Intestine OR Short Gut OR SBS) OR AB=(Short Bowel OR Small Intestine OR Short Intestine OR Short Gut OR SBS) Indexes=SCI‐EXPANDED Timespan=All years

#1 TI=(Teduglutide OR GLP‐2 OR Glucagon Like Peptide 2 OR Gattex OR Revestive OR ALX‐0600) OR AB=(Teduglutide OR GLP‐2 OR Glucagon Like Peptide 2 OR Gattex OR Revestive OR ALX‐0600) Indexes=SCI‐EXPANDED Timespan=All years

WHO ICTRP

Advanced Search

Short Bowel Syndrome OR Short Gut Syndrome in the Condition

Teduglutide in the Intervention

Recruitment status is ALL

Contributions of authors

MCR: formulated the research question and drafted the protocol.

GA: formulated the research question and drafted the protocol.

JCG: provided methodological expert opinion and reviewed the protocol.

LV: provided statistical expert opinion and reviewed the protocol.

LC: provided methodological expert opinion and reviewed the protocol.

MR: provided the search strategies and reviewed the protocol.

Sources of support

Internal sources

  • Research award from the Division of Paediatrics, Pontificia Universidad Católica de Chile, Chile

    Research award from the Division of Paediatrics, Pontificia Universidad Católica de Chile

External sources

  • No external  sources of support, Other

    No external  sources of support

Declarations of interest

MCR: None to declare.

GA: Educational event in the use of teduglutide in children, from Takeda.

JCG: None to declare.

LV: None to declare.

LC: None to declare.

MR: None to declare. 

These authors contributed equally to this work.

These authors contributed equally to this work.

New

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