Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID) Trial

N/AActive Not RecruitingNCT04095663

University of Washington255 enrolled

Overview

The COSMID (Comparison of Surgery and Medicine on the Impact of Diverticulitis) trial is a pragmatic, patient-level randomized superiority trial of elective colectomy vs. best medical management for patients with quality of life (QoL) limiting diverticular disease. A parallel observational cohort will include those who are disinclined to have their treatment choice randomized, but are willing to contribute information about their outcomes. The goal of the COSMID trial is to answer the question: For patients with QoL-limiting diverticular disease, is elective colectomy more effective than best medical management? The hypothesis being tested in the COSMID trial is that patient-reported outcomes (PROs) among patients in the surgery arm will be superior to those in the best medical management arm.

For over 50 years, professional society recommendations for the management of uncomplicated diverticulitis included early elective surgery to prevent the need for an emergency operation and avoid the risk of colostomy. Over the last 15 years the notion that a patient must have a certain number of episodes of acute uncomplicated diverticulitis (AUD) before undergoing elective colectomy has changed dramatically. This was, in part, due to studies showing that emergency surgery for complicated disease is much more likely to be needed during the first episode of diverticulitis, making the notion of prophylactic elective colectomy for AUD less relevant. Furthermore, clinicians realized that most recurrent episodes of AUD could be managed with outpatient antibiotics alone and that "best medical management" - including fiber supplementation, mesalazine, rifamycin and probiotics - could reduce symptoms between episodes of AUD. All of the components of best medical management have some, albeit limited, evidence of effectiveness, most in improving symptoms rather than reducing the risk of recurrence and are relatively safe and inexpensive. Best medical management is far less invasive than elective surgery but infrequently prescribed the US, in part because of limited insurance coverage. Alternatively, resection removes the diseased segment of colon, does relieve symptoms and decreases the risk of recurrence. In 2014, guidelines from the American Society of Colorectal Surgeons (ASCRS) abandoned "episode count" as an indication for surgery in patients with AUD and instead recommended individualizing the decision to operate for AUD based on the "effects on lifestyle (professional and personal) of recurrent attacks". Decision making about surgery in patients with lingering symptoms after recovery from an episode of AUD has not been the specific focus of an ASCRS guideline, but recommendations about elective surgery emphasize individualizing decision making based on the overall impact of the disease on the patient.These recommendations for individualization of treatment based on the quality of life (QoL) impact of recurrent AUD and lingering symptoms highlight the decision that hundreds of thousands of people now have to make each year. Based on the effect of the disease on their QoL they must choose between two very different treatment options: elective colectomy vs. best medical management. While the recommendation to individualize treatment based on the QoL impact is a step forward in advancing patient-centered care, the comparative effectiveness of these two treatments on symptoms and QoL has not been well studied. This will be a multi-site, open randomized trial in which participants with either recurrent AUD or lingering symptoms after an episode of AUD are randomized to one of two initial treatment strategies, elective segmental colectomy (performed laparoscopically when possible) and best medical management.

Interventions

Partial ColectomyPROCEDURE

Most partial colectomies are performed using a laparoscopic approach, when possible, and surgeons sometimes use a temporary, protective stoma if the re-connection is considered high risk.

Medical ManagementOTHER

Patients will be offered a varying combination of tools from the best medical management "toolbox" (diet and exercise, fiber supplementation/probiotics, and rifamycin/mesalazine) depending on what they have already tried. Based on the "evidence-based best medical toolbox" clinicians will be asked to consider rifamycin (dose/frequency) for those with AUD who are not responding to diet and exercise and mesalazine (dose/frequency) for those with lingering symptoms who are not responding to diet and exercise.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adults ≥18 years * At least one episode of diverticulitis confirmed by CT scan and a colonoscopy (completed or scheduled) to rule out or screen for other colon pathology concordant with screening guidelines * Persistent signs, symptoms, or concerns related to diverticulitis after recovery from an episode of left-sided diverticulitis as confirmed with self-reported QoL limitation. Exclusion Criteria: * Unable to consent in English or Spanish * Current diagnosis or previous endoscopic or surgical interventions for fistula, or stricture or current significant bleeding, related to diverticular disease * Last episode of acute diverticulitis currently unresolved (i.e., on antibiotics for diverticulitis; drain in place) * Previous operation for diverticulitis * Right-sided diverticulitis * Immunodeficiency (e.g., absolute neutrophil count \<500/mm3, chronic immunosuppressive drugs like oral corticosteroids, anti-TNF agents, or known AIDS \[i.e., recent CD4 count \<200\] assessed by patient history) * Actively undergoing chemotherapy or radiation for malignancy * Expectant or concurrent hemodialysis, peritoneal dialysis, treatments using indwelling venous catheters, or conditions putting patient at risk for bacterial seeding * Diagnosis of inflammatory bowel disease (i.e., Crohn's, ulcerative colitis) * Taking prescription medication for irritable bowel syndrome * Intolerance or allergy to all medications in the medical management arm * Comorbid or prior surgical conditions that contraindicate elective surgery (e.g., liver failure, renal failure, malignancy, "frozen abdomen") as determined by surgeon * Abdominal/pelvic surgery within the past month * Pregnant or expecting to become pregnant in the 30 days following baseline/screening * Unable to consent to research or self-respond to follow-up surveys (e.g., altered mental status) * Currently incarcerated in a detention facility or in police custody (patients wearing a monitoring device can be enrolled) at baseline/screening * Prior enrollment in the COSMID study or planning on enrollment in another investigational drug or vaccine while on study treatment * Unable or unwilling to return or be contacted for and/or complete research surveys.

Locations (29)

Cedars-Sinai Medical Center

Los Angeles, California, United States

UC San Diego Health

San Diego, California, United States

UCSF Health

San Francisco, California, United States

Stanford University Medical Center

Stanford, California, United States

University of Colorado

Denver, Colorado, United States

Outcomes

Primary Outcomes

Patient-reported quality of life as measured by Gastrointestinal Quality of Life Index (GIQLI)

A 36-item questionnaire assessing 5 domains: GI symptoms, physical function, emotional well-being, social well-being, and perception of medical treatment measured by a single item question. Each item has 5 response choices (i.e., all of the time, most of the time, some of the time, a little of the time, never). In addition, the measure produces an overall quality of life score (0-144) where higher numbers indicate greater QoL.

Time frame: Mean GIQLI at 6, 9, and 12 months following randomization to treatment

Secondary Outcomes

Diverticulitis Quality of Life (DV-QoL) instrument

A 17-item questionnaire including a pain scale and questions about about physical, emotional, and social effects of diverticulitis over the past 2 weeks, with a total score ranging from 0 (best) to 10 (worst) with higher scores reflecting worse quality of life effects from diverticulitis.

Time frame: Baseline, 12 months, 24 months

Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health measure

A 10-item instrument measuring domains that can be scored into a Global Physical Health component and Global Mental Health component. Each item includes 5 response choices, with the exception of the common 11-point pain intensity item ("How would you rate your pain on average?" with 0=no pain and 10=worst imaginable pain), where higher scores reflect more severe symptoms/impairment.

Time frame: Baseline; 6, 12, 24, 36 months

Decision Regret Scale

A 5-item validated questionnaire that measures regret among patients following a specific treatment decision. Scores range from 0-100 and higher scores reflect higher levels of regret. While developed for use in patients undergoing treatment for cancer, the questions are general in nature and adaptable to diverse clinical experiences.

Time frame: 6 and 36 months

Work Productivity and Activity Impairment instrument

A 6-item instrument used to measure the effect of general health and symptom severity on work productivity and regular activities during the past seven days. Scores are calculated applying algorithms to the five numerical responses, three of which are continuous variables (hours) and two of which are a scale from 0-10, then converting to a percentage, with higher WPAI scores indicating greater impairment and less productivity. The WPAI measures work productivity loss due to general health or a specified health problem. This questionnaire has been validated for use in many gastrointestinal diseases, including gastroesophageal reflux disease, irritable bowel syndrome, and Crohn's disease.

Time frame: Baseline; 6, 12, 18, 24, 30, 36 months