Study Preview
Study Title and Description
Mesalamine did not prevent recurrent diverticulitis in phase 3 controlled trials. -B(PREVENT2)
Key Questions Addressed
4 | KEY QUESTION 4 KQ 4: What are the effects, comparative effects, and harms of pharmacological interventions (e.g., mesalamine), non-pharmacological interventions (e.g., medical nutrition therapy), and elective surgery to prevent recurrent diverticulitis? • Do the (comparative) effects and harms vary by patient characteristics, course of illness, or other factors? |
Primary Publication Information
Title | Mesalamine did not prevent recurrent diverticulitis in phase 3 controlled trials. -B(PREVENT2) |
Author | Raskin JB., Kamm MA., Jamal MM., Márquez J., Melzer E., Schoen RE., Szalóki T., Barrett K., Streck P. |
Country | University of Miami Miller School of Medicine, Miami, Florida. Electronic address: JRaskin@med.miami.edu. |
Year | 2014 |
Numbers |
Pubmed ID: 25038431 |
Secondary Publication Information
There are currently no secondary publications defined for this study.
Extraction Form: Extraction Form for KQs 2 and 4
Arms
Number | Title | Description | Comments |
---|---|---|---|
1 | Placebo | ||
2 | Pharm: 5-ASA | AKA mesalazine, mesalamine 1.2 g/d | |
3 | Pharm: 5-ASA | AKA mesalazine, mesalamine 2.4 g/d | |
4 | Pharm: 5-ASA | AKA mesalazine, mesalamine 4.8 g/d |
Question... Follow Up | Answer | Follow-up Answer | |
---|---|---|---|
Specific KQ | KQ 2b: Antibiotics (acute) | ||
Study Design | RCT | ||
Country | USA | ||
Canada | |||
Germany | |||
Other ... | Brazil, Finland, Hungary, Italy, Netherlands, Romania, South Africa (from NCT) | ||
Funder | Industry (fully or in part) | ||
Study name | PREVENT2 | ||
Associated articles | |||
ClinicalTrials.gov identifier | NCT00545103 | ||
Start and end years of the Study | 2007 | ||
2011 | |||
Inclusion criteria | >= 18 years. 1 documented episodes of acute diverticulitis in the previous 24 months that resolved w/o colonic resection, and w/o signs/symptoms of diverticulitis within 6 wks of enrollment. Confirmation of diverticulosis via endoscopic evaluation of the sigmoid colon w/ at >= 3 diverticula noted. | ||
Exclusion criteria | Previous colorectal surgery, surgical intervention for diverticular disease (w/ exceptions of hemorrhoidectomy, colonic removal of polyps, appendectomy); no complicated diverticulitis (no perforation or fistulization present on CT); right-sided diverticulosis only; active peptic ulcer disease; history or current IBD. Active irritable bowel syndrome, GI bleeding, endometriosis or dysmenorrhea (6 months before baseline), or current or historical use of biologic drugs, immunomodulators, or systemic/rectal steroids (6 wks before baseline) (from NCT). | ||
Specific population? | No (all comers) | ||
Was diverticulitis diagnosed with CT? | CT | ||
If NRCS, what analytic method was used to account for differences between study arms? | |||
How was diverticulitis diagnosed | CT, MRI, ultrasound, colonoscopy, sigmoidoscopy, and barium enema. Endoscopic confirmation of 3 diverticula was required. | ||
Note/Comment about Design (or overall study) |
Baseline Characteristics
Question | Placebo | Pharm: 5-ASA | Pharm: 5-ASA | Pharm: 5-ASA | Total | Comments | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
Answer | Follow-up | Answer | Follow-up | Answer | Follow-up | Answer | Follow-up | Answer | Follow-up | ||
Participant race/ethnicity characteristics | Male | 49.3 | Male | 43.9 | Male | 51.7 | Male | 40.9 | Male | 46.4 | |
White | 94.4 | White | 93.9 | White | 93.2 | White | 94.6 | White | 94 | ||
Black | 3.5 | Black | 3.4 | Black | 3.4 | Black | 4.7 | Black | 3.8 | ||
Hispanic/Latino | 19 | Hispanic/Latino | 13.5 | Hispanic/Latino | 18.4 | Hispanic/Latino | 15.4 | Hispanic/Latino | 16.6 | ||
Asian | 0 | Asian | 0 | Asian | 0.7 | Asian | 0.7 | Asian | 0.3 | ||
Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 2.1 | Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 2.7 | Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 2.7 | Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 0 | Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 1.9 | ||
Participant Age - Continuous data (in years) | Mean | 55.7 | Mean | 57.8 | Mean | 54.2 | Mean | 56.7 | Mean | 56.1 | |
SD | SD | 10.88 | SD | 10.10 | SD | 11.76 | SD | 11.04 | |||
Participant Age - Categorical data | No data entered. | ||||||||||
Participants with Un/Complicated Diverticulitis | No data entered. | ||||||||||
Specific Complications of Diverticulitis | No data entered. | ||||||||||
Number of Prior Episodes of Diverticulitis (categorical) | 0 | 0.7 | 0 | 0 | 0 | 0 | 0 | 1.3 | 0 | 0.5 | |
1 | 61.3 | 1 | 64.2 | 1 | 56.5 | 1 | 57 | 1 | 59.7 | ||
2 | 22.5 | 2 | 20.3 | 2 | 25.2 | 2 | 22.8 | 2 | 22.7 | ||
Other_1 (include definition in %) | 4-5: 4.9 | Other_1 (include definition in %) | 4-5: 5.4 | Other_1 (include definition in %) | 4-5: 4.1 | Other_1 (include definition in %) | 4-5: 8.7 | Other_1 (include definition in %) | 4-5: 5.8 | ||
Other_2 (include definition in %) | 6-10: 2.1 | Other_2 (include definition in %) | 6-10: 2 | Other_2 (include definition in %) | 6-10: 2.7 | Other_2 (include definition in %) | 6-10: 0.7 | Other_2 (include definition in %) | 6-10: 1.9 | ||
History of (Prior) Complicated Diverticulitis | No data entered. | ||||||||||
KQ 4: Time Since Last Episode of Diverticulitis | Mean | 17.9 weeks | Mean | 16.5 weeks | Mean | 18.3 weeks | Mean | 13.9 weeks | Mean | 16.5 weeks | |
Range | 2-100 weeks | Range | 0-101 weeks | Range | 1-122 weeks | Range | 2-93 weeks | Range | 0-122 weeks | ||
Note/Comment about baseline characteristics | No data entered. | ||||||||||
Number of Prior Episodes of Diverticulitis (continuous) | No data entered. |
Results & Comparisons
Results Data
Outcome: Without recurrence Population: All Participants | Between-Arm Comparisons | ||||||||
---|---|---|---|---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA | Pharm: 5-ASA | Pharm: 5-ASA | Comparison Measure | Placebo vs. Pharm: 5-ASA | Placebo vs. Pharm: 5-ASA | Placebo vs. Pharm: 5-ASA |
104 weeks |
N Analyzed | 142 | 148 | 147 | 149 | 0.368 | 0.159 | 0.778 | |
Counts | 96 | 93 | 87 | 103 | |||||
Percentage | 67.6 | 62.8 | 59.2 | 69.1 |
Outcome: AE - Infection requiring Abx (CD II) Population: All Participants | |||||
---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA | Pharm: 5-ASA | Pharm: 5-ASA |
104 weeks |
N Analyzed | 142 | 148 | 147 | 149 |
Counts | 7 | 11 | 14 | 10 | |
Percentage | 4.9 | 7.4 | 9.5 | 6.7 |
Outcome: Adverse event - any Population: All Participants | |||||
---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA | Pharm: 5-ASA | Pharm: 5-ASA |
104 weeks |
N Analyzed | 142 | 148 | 147 | 149 |
Counts | 105 | 108 | 111 | 110 | |
Percentage | 73.9 | 73 | 75.5 | 73.8 |
Outcome: AE - Serious (SAE) Population: All Participants | |||||
---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA | Pharm: 5-ASA | Pharm: 5-ASA |
104 weeks |
N Analyzed | 142 | 148 | 147 | 149 |
Counts | 15 | 9 | 13 | 14 | |
Percentage | 10.56 | 6.08 | 8.84 | 9.40 |
Quality Dimensions
Dimension | Value | Notes | Comments |
---|---|---|---|
Q14: Cochrane - Random sequence generation (selection bias): Selection bias (biased allocation to interventions) due to inadequate generation of a randomized sequence | Low | Patients were randomly assigned in a 1:1:1:1 ratio. | |
Q15: Cochrane - Allocation concealment (selection bias): Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment | Low | Intervention assigned to each patient was determined by a computer generated fixed-block randomization schedule. | |
Q16: Cochrane - Blinding of participants (performance bias): Performance bias due to knowledge of the allocated interventions by participants during the study | Low | Double-blind | |
Q17: Cochrane - Blinding of personnel/ care providers (performance bias): Performance bias due to knowledge of the allocated interventions by personnel/care providers during the study. | Low | Double-blind | |
Q18: Cochrane - FOR OBJECTIVE OUTCOMES - Blinding of outcome assessor (detection bias): Detection bias due to knowledge of the allocated interventions by outcome assessors. | Yes | Low risk of detection bias because outcome assessors were blinded (NCT). | |
Q20: Cochrane - Incomplete outcome data (attrition bias): Attrition bias due to amount, nature or handling of incomplete outcome data | Low | Patients who completely withdrew from the study before week 104 without a protocol-defined recurrent of diverticulitis were considered dropouts and assumed to be treatment failures for the inter-to-treat primary analysis. Additional sensitivity analyses were performed using different methods for handling dropouts. Reasons for withdrawals are provided in Figure 1. | |
Q21: Cochrane - Selective Reporting (reporting bias): Reporting bias due to selective outcome reporting | Low | Study protocol is unavailable, but expected results | |
Q22: Cochrane - Other Bias: Bias due to problems not covered elsewhere in the table. If yes, describe them in the Notes. | Low | Study appears to be free of other sources of bias. | |
Q1: ROBINS-I 1.1 Is there potential for confounding of the effect of intervention in this study? | |||
Q3: ROBINS-I 1.4. Did the authors use an appropriate analysis method that controlled for all the important confounding domains? | |||
Q4: ROBINS-I 1.5. If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study? | |||
Q5: ROBINS-I 1.6. Did the authors control for any post-intervention variables that could have been affected by the intervention? | |||
Q6: ROBINS-I - Risk of bias judgement for BIAS DUE TO CONFOUNDING | |||
Q7: ROBINS-I 2.1. Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention? | |||
Q8: ROBINS-I 2.2. If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention? | |||
Q9: ROBINS-I 2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome? | |||
Q10: ROBINS-I 2.4. Do start of follow-up and start of intervention coincide for most participants? | |||
Q12: ROBINS-I 2.5. If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases? | |||
Q13: ROBINS-I - Risk of bias judgement for BIAS IN SELECTION OF PARTICIPANTS INTO THE STUDY | |||
Q2: Did the study divide the follow up time of each individual participant into the different interventions? | |||
Q11: Did the start and follow up calendar years coincide for most participants in the study? | |||
Q19: Cochrane - FOR SUBJECTIVE OUTCOMES - Blinding of outcome assessor (detection bias): Detection bias due to knowledge of the allocated interventions by outcome assessors. | Yes | Low risk of detection bias in patient-reported outcomes because participants were blinded. | |
Q23: NHLBI - Were eligibility/selection criteria for the study population prespecified and clearly described? | |||
Q24: NHLBI - Was the test/service/intervention clearly described and delivered consistently across the study population? | |||
Q25: NHLBI - Were the outcome measures prespecified, clearly defined, valid, reliable, and assessed consistently across all study participants? |
Quality Rating
No quality rating data was found.