Abstract
Background
This systematic review was performed to characterize the landscape of research conducted in patients with intestinal stoma (IS) and highlight unmet needs for clinical research in Crohn’s disease (CD) and IS.
Methods
We searched ClinicalTrials.gov from inception to May 25, 2022, to identify clinical trials assessing interventions in patients with an IS, as well as those with an IS and CD. Studies were grouped according to type of intervention. We excluded observational studies with no treatment arm.
Results
A total of 253 studies were included in the final analysis. Most studies investigated devices (n = 122 [48.2%]), or surgical procedures (n = 63 [24.9%]), followed by behavioral interventions (n = 30 [11.8%]), drugs (n = 20 [7.9%]), dietary interventions (n = 2 [0.8%]), skin care products (n = 2 0.8%]), and others (n = 14 [5.5%]). A total of 50.9% (n = 129) of studies had completed recruitment, enrolling 11 116 participants. Only 6 studies (surgery: n = 3; physiological studies: n = 2; drugs: n = 1) exclusively included patients with inflammatory bowel disease (IBD), and 16 studies commented that patients with IBD were excluded in their eligibility criteria. No study assessed efficacy of drugs in patients with CD and IS. Approximately one-quarter of studies (n = 65 of 253) included quality of life as an outcome measure.
Conclusion
There is a paucity of research in IBD patients with IS, with the majority focusing on devices and surgical procedures. There have been no drug trials evaluating efficacy in patients with CD and IS. There is an urgent need to identify barriers to enrollment and develop eligibility and outcome measures that enable the inclusion of patients with CD with stoma into clinical trials.
Keywords: ileostomy, intestinal stoma, Crohn’s, ulcerative colitis
Key Messages.
What is already known?
High-quality evidence is lacking for the management of patients with Crohn’s disease and intestinal stoma.
What is new here?
We reviewed registered interventional trials for patients with intestinal stoma in ClinicalTrials.gov. While most studies investigated devices and surgical procedures, there were minimal interventional studies in patients with Crohn’s disease and intestinal stoma.
How can this study help patient care?
With our study we highlight key unmet needs in ostomy research and identify the major trends in this field.
Introduction
Fecal diversion is a surgical procedure by which an artificial opening or stoma is created in the colon or small bowel to divert feces outside the abdominal wall.1 The fecal diversion is indicated for a diverse range of gastrointestinal conditions, the most common of which are gastrointestinal malignancy, inflammatory bowel disease (IBD), diverticulitis, bowel obstruction, high-risk anastomosis, and complicated gastrointestinal surgery. It is estimated that approximately two-thirds of patients with Crohn’s disease (CD) will require surgery in their lifetime and, therefore, are inherently at risk for temporary or permanent stoma. Patients with ulcerative colitis (UC) are also at risk of having temporary stoma surgery before ileal pouch–anal anastomosis formation. Permanent ileostomy (PI) in patients with CD is typically considered in cases of medically refractory ileocolonic or colonic disease following subtotal or total proctocolectomy. The annual risk of intestinal stoma (IS) in patients with CD undergoing surgery is 1.8 stomas per 100 person years,2 and the 5-year cumulative risk of having stoma surgery was 2.5% in a population-based study.3 The impact of emerging biological therapies on rates of IS formation is unclear. In the prebiologic era, the cumulative risk of receiving any IS and permanent stoma were 41% and 14% in 20 years, respectively.4 Although observational studies showed a decrease in IS formation, 2 population-based studies from Sweden and Canada showed no decrease in incidence of IS formation within 5 years of CD diagnosis between 2003 to 2019 and no decrease in elective stoma formation between 2002 to 2011, respectively.2,3
A considerable proportion of patients with an IS experience complications and the reported incidence rates of stomal and peristomal complications varies from 21% to 70%, with repeat surgery required in one-fifth of cases.5 Apart from mechanical and psychological complications related to creation of an IS, patients with CD and PI can develop additional disease-related complications such as CD recurrence in the small bowel proximal to the IS, peristomal pyoderma gangrenosum, enterocutaneous fistulae around the IS, and strictures or adhesions causing intestinal obstruction. It is estimated that approximately one-third of patients with CD and PI experience disease recurrence in the small bowel proximal to the IS, which may necessitate subsequent medical therapy, and 16% experience significant recurrence requiring further surgery.6 Unfortunately, patients with IS are universally excluded from CD pharmaceutical trials,7 and high-quality evidence is lacking in this group of patients to guide physicians in providing optimal therapy. We aimed to explore the landscape of interventional trials registered in ClinicalTrials.gov with an aim to assess trends in clinical research on patients with ileostomy or colostomy irrespective of primary diagnosis and also to evaluate interventional studies that particularly focused on patients with CD with PI.
Methods
We searched ClinicalTrials.gov from inception to May 25, 2022, to identify studies assessing patients with IS. We searched the database for terms including: “ostomy,” “ileostomy,” “colostomy,” and “stoma.” Given that all studies in ClinicalTrials.gov were in English, there were no language restrictions in our search.
Study Selection
Eligibility assessment was performed independently by 2 investigators (S.K.V. and T.S.). We included interventional studies assessing both medical and nonmedical therapies. We excluded observational studies with no treatment arm. Disagreements were resolved by consensus among the author team, or through arbitration by a third author (V.J.).
Data extraction and analysis
Data were extracted by 3 authors (S.K.V., T.S., and T.M.N.) onto a Microsoft Excel form. The studies were grouped a priori into 7 different categories according to the specific type of intervention that they evaluated: drug trials, device trials, dietary trials, behavioral trials, surgical or procedural trials, skin care trials, and others. The following characteristics were extracted for each study: NCT number, type of study, year, country of origin, center(s) (single center/multicenter), recruitment status (recruiting, active not recruiting, completed, withdrawn/terminated), study design, study phase, disease/condition, type of stoma, type of intervention, comparator, included ages, inclusion criteria, primary outcome, secondary outcome, length of follow-up, number of patients recruited, and whether the results are posted. Statistical analysis and the development of the figures were performed in Microsoft Excel.
Results
The search yielded 580 studies with 234 duplicates, leaving 346 studies to screen. Of these 346 studies, a total of 253 interventional studies met our inclusion criteria after excluding 93 studies for various reasons (Supplementary Figure 1 and Supplementary Table 1).
Study characteristics and population
Characteristics of included studies are presented in Table 1. Of the 253 interventional studies, 71.1 % (n = 180) were randomized controlled trials (RCTs). Most of the interventions were devices (48.2% [n = 122]) and surgical procedures (24.9% [n = 63]), followed by behavioral interventions (11.8% [n = 30]), drugs (7.9% [n = 20]), dietary interventions (0.8% [n = 2]), skin care products (0.8% [n = 2]), and others (5.5% [n = 14]). A total of 50.9% (n = 129) of studies had completed recruitment, with a total of 11 116 participants. A total of 28.4% (n = 72) of studies were indicated as actively recruiting, and 20.5% (n = 52) of studies had withdrawn/terminated/unknown status. The majority of studies (78.2% [n = 198]) were conducted in North America and in European countries (Figure 1). A total of 92.5% (n = 234) of the studies included predominantly adult participants 18 years of age and older, and 2.3% (n = 6) recruited exclusively pediatric patients. A total of 58.5% (n = 148) of studies included patients with ileostomy, and 13.8% (n = 35) included patients with colostomy, whereas 27.7% (n = 70) of recruited patients could have either ileostomy or colostomy. While majority of studies (71.5% [n = 181]) included patients with more than 1 disease, 23.7% (n = 60) exclusively included patients with stoma for gastrointestinal malignancy (Figure 2).
Table 1.
Characteristics of registered interventional studies of intestinal stoma.
| Study characteristic | Result |
|---|---|
| Phase of the trial | |
| 1 | 8 (3.2) |
| 2 | 15 (5.9) |
| 3 | 22 (8.7) |
| 4 | 11 (4.3) |
| Not reported or not applicable | 197 (77.9) |
| Centers | |
| Single center | 180 (71.1) |
| Multicenter | 67 (26.5) |
| Not reported | 6 (2.4) |
| Age of eligible participants | |
| <18 y (pediatric) | 6 (2.4) |
| ≥18 y | 234 (92.5) |
| All ages | 13 (5.1) |
| Recruitment status of the studies | |
| Completed | 129 (51.0) |
| Active (not recruiting) | 33 (13.0) |
| Active (recruiting) | 39 (15.4) |
| Withdrawn/terminated | 37 (14.6) |
| Unknown | 15 (5.9) |
| Intervention type | |
| Drug | 20 (7.9) |
| Device | 122 (48.2) |
| Dietary | 2 (0.8) |
| Behavioral | 30 (11.9) |
| Surgical/Procedural | 63 (24.9) |
| Skin care | 2 (0.8) |
| Other | 14 (5.5) |
| Study design | |
| Randomized controlled trial | 180 (71.1) |
| Nonrandomized trial | 15 (5.9) |
| Single-group interventional trial | 58 (22.9) |
| Comparator type | |
| Placebo | 7 (2.8) |
| Active comparator | 109 (43.1) |
| Standard of care | 56 (22.1) |
| No comparator | 77 (30.4) |
| Not reported | 4 (1.6) |
| Type of stoma | |
| Colostomy | 35 (13.8) |
| Ileostomy | 148 (58.5) |
| Colostomy or ileostomy | 70 (27.7) |
| Number of trials excluding CD/UC patients | 16 (6.3) |
| Number of trials assessing decreased stoma output | 8 (3.1) |
| Number of studies that included exclusively patients with IBD | 6 (2.3) |
Values are n (%).
Abbreviations: CD, Crohn’s disease; IBD, inflammatory bowel disease; UC, ulcerative colitis.
Figure 1.
Pie chart showing geographical distribution of registered interventional studies.
Figure 2.
Pie chart showing disease distribution of included studies.
Types of Interventional studies
Device trials
There were 122 studies that were registered between 2001 and May 2022. Of these, 65.6% (n = 80 of 122) completed recruitment, enrolling 7207 participants, and 16.4% (n = 20 of 122) studies were listed as active or recruiting, while 18% (n = 22 of 122) were terminated or withdrawn or had unknown status. The majority of device trials were conducted in European countries (68.8% [n = 84 of 122]), especially in Denmark (n = 47 of 84). Most were RCTs (60.5% [n = 74 of 122]) and included patients with ileostomy (56.5% [n = 69 of 122]). A total of 66.4% (n = 81 of 122) of studies focused on ostomy appliances and related products (eg, new ostomy pouch and adhesive strips, bag filters, base plate, ostomy belt). A total of 17.2% (n = 21 of 122) of studies investigated different kinds of mesh to prevent parastomal hernia. The remaining studies investigated adhesion barrier films, continence control devices, incisional wound management systems, ostomy button, surgical sealant, bridge device, and collectable tube ileostomy. The primary outcomes of these device studies were related to safety and device function including leakage around the stoma bag, patient preference, and rate of para stomal hernia formation. Only 3 studies assessed quality of life.
Behavioral intervention trials
Thirty studies investigated behavioral interventions that were registered between 2010 to 2022. Of these, 40% (n = 12 of 30) of studies had completed recruitment, enrolling 1237 participants, 53.3% (n = 16 of 30) of studies were listed as active (either recruiting or not yet started), and 2 studies were withdrawn. A total of 66.7% (n = 20 of 30) of studies were RCTs. A total of 13.3% (n = 4 of 30) of studies included colostomy, with 16.7% (n = 5 of 30) including ileostomy, and 70% (n = 21 of 30) of studies included patients with either ileostomy or colostomy. A total of 46.7% (n = 14 of 30) of studies focused predominantly on pre- and/or postoperative education, and 33.4% (n = 10 of 30) of studies focused on predominantly postoperative monitoring and care. Only one study assessed interventions for sexual readjustment. One study included patients undergoing stoma closure, which assessed the efficacy of pelvic floor exercises on bowel evacuation habits following stoma closure. One study assessed the efficacy of abdominal muscle training to prevent parastomal hernia repair. A total of 43.4% (n = 13 of 30) of studies assessed quality of life as the primary outcome. Other primary outcome measures were related to patient participation, self-care ability, sexual function, hospitalizations, and rate of parastomal hernia.
Drug trials
Twenty studies were included that assessed pharmacological interventions that were registered between 2012 and 2021. Of these, 45% (n = 9 of 20) completed enrolling 343 participants. All studies except 2 included patients with ileotomy. A total of 40% (n = 8 of 20) of studies investigated pharmacological interventions (loperamide, teduglutide, lanreotide, amino acid–based supplement, hydrolyzed whey, oral rehydration solution, and hydrolyzed guar gum) that were intended to reduce stoma output. Four studies assessed probiotics, and 2 studies each investigated bupivacaine and tincture of opium. The remaining 3 studies evaluated recombinant interleukin-12, oral rehydration solution, and short-chain fatty acid irrigation. The major primary outcomes assessed were efficacy and safety of the study drugs, and none of the studies assessed quality of life as a primary outcome.
Procedural trials
There were 63 procedural trials that were registered between 2001 and 2022. Only 28.5% (n = 18 of 63) of studies were listed as complete, enrolling 2126 participants, 30% (n = 19 of 63) of studies were withdrawn or had unknown status, and 41.2% (n = 26 of 63) of the studies are currently active or recruiting. A total of 65% (n = 41 of 63) of the studies included patients with ileostomy, and 19% (n = 12 of 63) included patients with colostomy, and the remaining studies (n = 10 of 63) included both. A total of 36.5% (n = 23 of 63) of the studies had focused on procedures related to stoma creations, while 36.5% (n = 23 of 63) on had focused on stoma reversal. The remaining studies (27% [n = 17 of 63]) assessed stimulation techniques, anesthesia, parastomal hernia, timing of discharge, bowel preparation prior to stoma surgery, wound dressing, and tailored use of defunctioning stoma. The primary outcomes were complications, morbidity, mortality, hospitalizations, rate of parastomal hernia, duration of hospital stay, postoperative ileus, and safety. Only 5 studies assessed quality of life as a primary outcome.
Skin care products
Only 2 studies assessed skin care products, of which one study was withdrawn and one is active but not recruiting.
Dietary interventions
There were only 2 dietary interventional trials, and both are currently recruiting. One study assessed a low-fiber diet vs a regular diet in postoperative colorectal patients with ileostomies and one evaluated enteral nutrition in infants with ileostomy.
Other interventional studies
There were 14 studies that could not be categorized into one of the previous interventions. Among them, 5 interventional studies assessed absorption of beta-carotene, carotenoids, cocoa flavanols, milk polar lipids, and broccoli phytochemicals. Two studies assessed the metabolic effect of intraileal glucose and bile salts. Two studies assessed the effect of esomeprazole and SYN-004 on degradation of ceftriaxone in patients with ileostomy. One study each assessed the effect of anal dilatation and probiotics in preventing anterior resection syndrome, the role of stool application in prevention of perianal maceration in children, the digestibility of selected resistant starches the role of chewing gum on postoperative ileus, and an artificial intelligence–based algorithm to make a decision on the type of stoma that should be created.
Studies assessing quality of life as an outcome measure
Out of 253 studies, 65 included quality of life as an outcome measure. Of these, 18 studies included quality of life as the primary outcome, 43 included it as a secondary outcome, and 4 included it as both a primary and secondary outcome measure. A total of 19 different scores were used for assessing quality of life. Only 22 studies included scores specific for stoma patients (Table 2).
Table 2.
Studies that assessed QOL as an outcome with details on type of outcome measures used.
| Study identification number | Year of registration | Type of intervention | QOL questionnaire | Specific for stoma |
|---|---|---|---|---|
| NCT04824287 | 2018 | Behavioral intervention | SF-36 | No |
| NCT04492007 | 2020 | Behavioral intervention | Functional Assessment of Cancer Therapy–General | No |
| NCT05344950 | 2022 | Behavioral intervention | Functional Assessment of Cancer Therapy–General | No |
| NCT01403883 | 2011 | Behavioral intervention | SF-36 | No |
| NCT05076669 | 2021 | Behavioral intervention | Stoma QOL questionnaire | Yes |
| NCT04943822 | 2021 | Behavioral intervention | Enterostomy QOL | Yes |
| NCT01154725 | 2010 | Behavioral intervention | Ostomy Adjustment Scale and SF-36 | Yes |
| NCT02658123 | 2016 | Behavioral intervention | Not specified | No |
| NCT02526264 | 2015 | Behavioral intervention | EORTC QLQ-CR30 and EORTC QLQ-CR29 | No |
| NCT01600508 | 2011 | Behavioral intervention | EQ-5D | No |
| NCT03913715 | 2019 | Behavioral intervention | COH-QOL-OQ | Yes |
| NCT04561674 | 2017 | Behavioral intervention | COH-QOL-OQ | Yes |
| NCT04375930 | 2019 | Behavioral intervention | Stoma QOL questionnaire | Yes |
| NCT04272528 | 2020 | Behavioral intervention | Stoma QOL questionnaire | Yes |
| NCT04682028 | 2021 | Behavioral intervention | Stoma QOL questionnaire | Yes |
| NCT04701853 | 2021 | Behavioral intervention | Stoma QOL questionnaire | Yes |
| NCT02036268 | 2012 | Behavioral intervention | Stoma QOL questionnaire and Stoma Self-Efficacy Scale | Yes |
| NCT04675606 | 2020 | Diet | GQLI | No |
| NCT04688242 | 2021 | Othersa | EORTC QLQ-CR29 | No |
| NCT04795180 | 2013 | Drugs | SF-36 | No |
| NCT03451253 | 2018 | Drugs | IBDQ and SF 36 | No |
| NCT00626821 | 2008 | Device | Stoma QOL questionnaire | Yes |
| NCT04868617 | 2021 | Device | DLQI | No |
| NCT04202666 | 2020 | Device | Ostomy Appliance Satisfaction Questionnaire and life quality stomy care questionnaire | Yes |
| NCT01317485 | 2010 | Procedure | SF-36, EQ-5D, and GQLI | No |
| NCT01766661 | 2013 | Procedure | COREFOQ | No |
| NCT05163873 | 2021 | Procedure | EQ-5D | No |
| NCT05284864 | 2022 | Procedure | SF-36 | No |
| NCT01287637 | 2011 | Procedure | EORTC QLQ-CR30 and EORTC QLQ-CR29 | No |
| NCT02665026 | 2016 | Procedure | Not specified | No |
| NCT03746353 | 2018 | Procedure | FACIT-C format | No |
| NCT04569331 | 2020 | Procedure | EORTC QLQ-CR29 | No |
| NCT00428636 | 2001 | Procedure | GQLI | No |
| NCT03397901 | 2018 | Procedure | EORTC QLQ-CR30 | No |
| NCT04357171 | 2012 | Procedure | SF-36 | No |
| NCT04372992 | 2020 | Procedure | EORTC QLQ-CR29, EQ-5D | No |
| NCT02090985 | 2013 | Procedure | Not specified | No |
| NCT00457327 | 2006 | Procedure | Not specified | No |
| NCT05233787 | 2022 | Procedure | EORTC QLQ-CR30 | No |
| NCT00959738 | 2008 | Procedure | Stoma QOL questionnaire | Yes |
| NCT04604730 | 2021 | Procedure | EQ-5D | No |
| NCT03796702 | 2011 | Procedure | EORTC QLQ-CR30 | No |
| NCT04326335 | 2020 | Device | Stoma QOL questionnaire | Yes |
| NCT02609451 | 2007 | Procedure | GQLI | No |
| NCT03587519 | 2018 | Procedure | PROMIS questionnaire | No |
| NCT02238964 | 2012 | Device | EQ-5D | No |
| NCT02472639 | 2015 | Device | Stoma QOL questionnaire | Yes |
| NCT04916067 | 2021 | Device | PROMIS short form 2.0 | No |
| NCT03750461 | 2019 | Device | PROMIS short form 2.0 | No |
| NCT03750942 | 2019 | Device | EQ-5D, Carolinas Comfort Scale, EORTC QLQ-CR29 | No |
| NCT02756273 | 2016 | Device | Stoma QOL questionnaire | Yes |
| NCT02121743 | 2014 | Device | Stoma QOL questionnaire | Yes |
| NCT04802538 | 2020 | Device | Ostomy questionnaire score | Yes |
| NCT03982875 | 2019 | Device | Patient-reported QOL | No |
| NCT05072379 | 2021 | Behavioral intervention | WHOQOL-BREF questionnaire | No |
| NCT03781206 | 2019 | Device | EQ-5D | No |
| NCT00908661 | 2007 | Device | SF-36 | No |
| NCT00917995 | 2008 | Device | Not specified | No |
| NCT00771407 | 2008 | Device | Stoma QOL questionnaire | Yes |
| NCT04715893 | 2021 | Device | Stoma QOL questionnaire | Yes |
| NCT03445936 | 2018 | Device | RAND-36 survey | No |
| NCT02576184 | 2015 | Device | SF-36 | No |
| NCT02223104 | 2013 | Device | Stoma QOL questionnaire | Yes |
| NCT02602236 | 2015 | Device | Stoma QOL questionnaire | Yes |
| NCT02896686 | 2016 | Device | SF-36 | No |
Abbreviations: COH-QOL-OQ, City of Hope–Quality of Life–Ostomy Questionnaire; COREFOQ, Colorectal Functional Outcome Questionnaire; EORTC QLQ CR, European Organization for Research and Treatment of Cancer Colorectal Quality of Life Module; DLQI, Dermatology Life Quality Index; FACIT-C, Functional Assessment of Chronic Illness Therapy–Colorectal; GQLI, Gastrointestinal Quality of Life Index; IBDQ, Inflammatory Bowel Disease Questionnaire; PROMIS, Patient-Reported Outcomes Measurement Information System; QOL, quality of life; SF-36, 36-Item Short Form Survey; WHOQOL-BREF, World Health Organization Quality of Life–Brief Version.
aAnal dilatation and probiotics prior to ileostomy in patients undergoing proctectomy.
Interventional studies in patients with IBD
Out of 253 studies, while 16 studies commented that that they excluded patients with IBD in the eligibility criteria, only 6 of them exclusively included patients with IBD. Of these, one study (phase 1) included patients with CD, assessing the safety and tolerability of oral anti-tumor necrosis factor drug (V565), and 2 studies included patients with ulcerative colitis (UC), assessing the need for loop ileostomy after pouch formation, or timing of ileostomy reversal following ileal pouch–anal anastomosis. The remaining 3 studies included both patients with UC and CD; of these, 2 studies investigated the effect of iso-osmolar oral supplement and amino acid–based beverage on stoma output, and one study investigated mesh implantation to prevent parastomal hernia.
Temporal trends
The temporal trends of stoma clinical trials are presented in Figure 3. There has been a consistent increase in the number of trials registered in the last 10 years. Between 2001 and 2010, there were 31 interventional trials registered, 96 trials were registered between 2011 and 2015, and 125 trials were registered from 2016 until the search date of our study. Of these, device (n = 55), procedural (n = 29), and behavioral interventional trials (n = 21) constitute more than 84% of trials.
Figure 3.
Graph showing temporal trend of registered interventional studies of patients with intestinal stoma.
Discussion
It is estimated that more than 1 million people are currently living with an IS in North America.8 Patients living with an IS may face specific physical as well as psychological challenges. Several gastrointestinal diseases are risk factors for creation of an IS, particularly patients with CD who have a high lifetime risk of intestinal resection despite the best available pharmacological therapies.9 A significant proportion of patients with CD and PI are at subsequent high risk of recurrence in the residual small bowel proximal to stoma.10 Thus, patients with CD living with PI are a special subgroup of patients who experience not only stoma-related complications, but also disease-related complications.11 In this review, we provide a cross-sectional assessment of the interventional trial landscape for stoma research in general as well as for stoma specific to CD with PI. According to our study, the majority of registered interventional trials (70%) involving patients living with IS focused predominantly on external appliances and surgical procedures.
Ostomies can impact patients in different domains of life such as quality of life, sexual intimacy, self-esteem, occupation, and social interactions and pose significant financial burden on patients.12,13 As a result, about two-thirds of patients have been reported to avoid physical and social activities,14 and patients with IS are at increased risk of psychological comorbidity such as adjustment disorder, depression, and anxiety.15–17 In our study, we found that only 7% of registered studies evaluated quality of life as a primary outcome, and 17% of studies evaluated it as a secondary outcome. Appropriate pre- and postoperative educational interventions have been shown to be associated with better acceptability of the IS and are universally recommended by the major international ostomy guidelines.18–20 It should be acknowledged that in patients with CD, quality of life could be influenced by disease behavior prior to stoma surgery. For example, patients with complicated refractory disease course with multiple hospital admissions may perceive significant improvement in quality of life after stoma surgery as a result of better disease control.21 Thus, quality-of-life assessment instruments that are specific to patients with CD and PI should be developed. Other important areas that are neglected are diet, interventions reducing stoma output, and behavioral interventions addressing sexual intimacy problems. In our analysis, we found only one study that assessed sexual intimacy. Therefore, new studies addressing these domains should be designed and actively investigated.
Various international societies offer moderate to high quality guidelines on adequate management of patients living with ostomy. A group of researchers assessed the quality of clinical practice guidelines for ostomy care by using the AGREE-II (Appraisal of Guidelines, Research and Evaluation–II) tool,22 and the authors reported that among the quality domains, scope and purpose was rated highest (87.78%). Unfortunately, the applicability of these guidelines was only 55.42%, indicating that there is need for improvement and unanswered issues to address.23 Moreover, the majority of recommendations in these guidelines are based on low-quality evidence.20 Another important observation was that the majority of the studies were single-center studies and conducted in North America and Europe, indicating that there is a need for studies to include patients from different geographic locations and with more diverse ethnicities.
We identified only 6 studies that exclusively included patients with IBD. Among these, 2 studies were physiological studies, 1 assessed the safety of an oral anti-tumor necrosis factor drug, 2 were related to stoma closure, and 1 investigated the need for diverting loop ileostomy in patients undergoing ileal pouch–anal anastomosis. However, none of the studies assessed efficacy of other pharmacotherapies in patients with CD and PI, indicating the need for further research in this area.
While it may be surprising that no studies enrolling patients with CD and PI were identified, it should be acknowledged that clinical trial recruitment of CD patients with PI is challenging, as there are no validated tools available to assess disease activity for this special population. Commonly used clinical outcome measures like Crohn’s Disease Activity Index, Harvey-Bradshaw index, and Patient-Reported Outcomes–2 based on stool frequency may not be appropriate for patients with PI, nor do they adequately capture the burden of patient symptomatology. Additionally, the operating characteristics of currently available endoscopic instruments like the Crohn’s Disease Endoscopic Index of Severity and the Simple Endoscopic Score for Crohn’s Disease have not been evaluated in patients with CD and PI, which poses significant challenges in determining endoscopic outcomes for these patients in clinical trials. Disease activity assessment of terminal ileum proximal to stoma using these scores may be useful, similar to that in patients with isolated terminal ileal CD. However, this needs to be validated.
We acknowledge key limitations of our study. First, our study included only studies registered in one database. Therefore, studies from Europe and Asia that are registered in other regional clinical trial registries but not on ClinicalTrials.gov may have been missing. However, currently over 433 000 studies from 221 countries are registered in ClinicalTrials.gov; thus, we believe that the search was likely to have captured most studies. Second, ClinicalTrials.gov was made available only in 2000, but it was not until 2005 that the International Committee of Medical Journal Editors began mandating trial registration for publication. Therefore, it is possible that interventional trials that were done before 2005 may have been missed in our study. Third, incomplete information of the trials may have led to misclassification of outcomes and studies. Nonetheless, this review provides a comprehensive examination of ostomy clinical trials, by assessing the study design, indications, interventions, eligibility criteria, and primary outcomes. With our study, we highlight key unmet needs in ostomy research and identify the key trends in this field. To our knowledge, this is the first systematic review to assess treatment trends in ostomy patients.
Conclusions
There is a paucity of research that has been conducted in patients with IS, with the majority focusing on devices and surgical procedures, with very few interventions addressing patient quality of life. There have been no pharmaceutical studies assessing efficacy in patients with CD and IS. This study highlights an urgent need to identify barriers to enrollment and to develop eligibility and outcome measures that enable the inclusion of patients with CD with stoma into clinical trials.
Supplementary data
Supplementary data is available at Inflammatory Bowel Diseases online.
Contributor Information
Sudheer K Vuyyuru, Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, ON, Canada.
Christopher Ma, Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
Tanmay Sharma, Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, ON, Canada.
Tran M Nguyen, Lawson Health Research Institute, Western University, London, ON, Canada.
Talat Bessissow, Division of Gastroenterology, Department of Medicine, McGill University Health Center, Montreal, QC, Canada.
Neeraj Narula, Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
Siddharth Singh, Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Florian Rieder, Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Vipul Jairath, Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, ON, Canada; Lawson Health Research Institute, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
Funding
None received.
Conflicts of Interest
C.M. has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Roche, and Sanofi; speaker fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; and research support from Ferring, Takeda, and Pfizer. T.B. has served as a speaker or advisor for AbbVie, Alimentiv (formerly Robarts Inc), Amgen, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Gilead, Iterative Scopes, Janssen, Pendopharm, Merck, Pentax, Pfizer, Roche, Sandoz, Takeda, and Viatris. N.N. has served as a speaker or advisor for Janssen, AbbVie, Takeda, Pfizer, Merck, Sandoz, Fresenius Kabi, Innomar, Iterative Scopes, Bristol Myers Squibb, Viatris and Ferring. S.S. has received institutional research support from Pfizer and AbbVie (in the last 24 months); and personal fees from Pfizer for ad hoc grant review. F.R. has served as a consultant for Adnovate, Agomab, Allergan, AbbVie, Arena, Boehringer Ingelheim, Celgene/BMS, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Janssen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Surmodics, Surrozen, Takeda, Techlab, Theravance, Thetis, UCB, Ysios, and 89Bio. V.J. has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion; and speaker fees from AbbVie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi. The other authors disclose no conflicts.
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