Study Preview
Study Title and Description
Mesalamine did not prevent recurrent diverticulitis in phase 3 controlled trials.-A
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.-A |
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 (1.2 g/d) | ||
3 | Pharm: 5-ASA (2.4 g/d) | ||
4 | Pharm: 5-ASA (4.8 g/d) |
Question... Follow Up | Answer | Follow-up Answer | |
---|---|---|---|
Specific KQ | KQ 2b: Antibiotics (acute) | ||
KQ 2b: Antibiotics (acute) | |||
KQ 2b: Antibiotics (acute) | |||
Study Design | RCT | ||
RCT | |||
RCT | |||
Country | USA | ||
UK | |||
Other ... | Argentina, Australia, Colombia, France, India, Israel, New Zealand, Spain, Sweden (from NCT) | ||
Funder | Industry (fully or in part) | ||
Study name | PREVENT1 | ||
Associated articles | |||
ClinicalTrials.gov identifier | NCT00545740 | ||
Start and end years of the Study | 2007 | ||
2013 | |||
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 | Endoscopic confirmation of >= 3 diverticula was required. CT, MRI, ultrasound, colonoscopy, sigmoidoscopy, and barium enema. | ||
Note/Comment about Design (or overall study) |
Baseline Characteristics
Question | Placebo | Pharm: 5-ASA (1.2 g/d) | Pharm: 5-ASA (2.4 g/d) | Pharm: 5-ASA (4.8 g/d) | Total | Comments | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
Answer | Follow-up | Answer | Follow-up | Answer | Follow-up | Answer | Follow-up | Answer | Follow-up | ||
Participant race/ethnicity characteristics | Male | 48.3 | Male | 55.2 | Male | 51.7 | Male | 52.7 | Male | 52.8 | |
White | 83 | White | 79 | White | 83.2 | White | 82 | White | 81.8 | ||
Black | 1.4 | Black | 3.5 | Black | 1.4 | Black | 2.7 | Black | 2.2 | ||
Hispanic/Latino | 20.4 | Hispanic/Latino | 25.9 | Hispanic/Latino | 25.9 | Hispanic/Latino | 21.3 | Hispanic/Latino | 23.3 | ||
Asian | 2.7 | Asian | 2.8 | Asian | 2.1 | Asian | 2 | Asian | 2.4 | ||
Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 12.9 | Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 14.7 | Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 13.3 | Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 13.3 | Other (or specific) race/ethnicity 1 - include race/ethnicity in parentheses | 13.6 | ||
Participant Age - Continuous data (in years) | Mean | 57.1 | Mean | 55.1 | Mean | 54.5 | Mean | 54.5 | Mean | 55.3 | |
SD | 10.42 | SD | 11.11 | SD | 11.96 | SD | 11.93 | SD | 11.39 | ||
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 | 0 | 0 | 0 | 1.4 | 0 | 0 | 0 | 0.3 | |
1 | 60.5 | 1 | 55.9 | 1 | 60.1 | 1 | 56 | 1 | 58.1 | ||
2 | 23.1 | 2 | 29.4 | 2 | 22.4 | 2 | 26.7 | 2 | 25.4 | ||
Other_1 (include definition in %) | 4-5: 4.8 | Other_1 (include definition in %) | 4-5: 5.6 | Other_1 (include definition in %) | 4-5: 7.7 | Other_1 (include definition in %) | 4-5: 4.0 | Other_1 (include definition in %) | 4-5: 5.5 | ||
Other_2 (include definition in %) | 6-10: 2.7 | Other_2 (include definition in %) | 6-10: 1.4 | Other_2 (include definition in %) | 6-10: 1.4 | Other_2 (include definition in %) | 6-10: 2.7 | Other_2 (include definition in %) | 6-10: 2.1 | ||
History of (Prior) Complicated Diverticulitis | No data entered. | ||||||||||
KQ 4: Time Since Last Episode of Diverticulitis | Median | 14.7 weeks | Median | 12 weeks | Median | 12.9 weeks | Median | 13.6 weeks | Median | 13 weeks | |
Range | 0-94 weeks | Range | 1-419 weeks | Range | 1-93 weeks | Range | 1-114 weeks | Range | 0-419 weeks | ||
Note/Comment about baseline characteristics | No data entered. | ||||||||||
Number of Prior Episodes of Diverticulitis (continuous) | No data entered. |
Results & Comparisons
Results Data
Outcome: No recurrence Population: All Participants | Between-Arm Comparisons | ||||||||
---|---|---|---|---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA (1.2 g/d) | Pharm: 5-ASA (2.4 g/d) | Pharm: 5-ASA (4.8 g/d) | Comparison Measure | Placebo vs. Pharm: 5-ASA (1.2 g/d) | Placebo vs. Pharm: 5-ASA (2.4 g/d) | Placebo vs. Pharm: 5-ASA (4.8 g/d) |
104 weeks |
N Analyzed | 147 | 143 | 143 | 150 | 0.780 | 0.741 | 0.047 | |
Counts | 95 | 89 | 90 | 79 | |||||
Percentage | 64.6 | 62.2 | 62.9 | 52.7 |
Outcome: Adverse event - any Population: All Participants | |||||
---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA (1.2 g/d) | Pharm: 5-ASA (2.4 g/d) | Pharm: 5-ASA (4.8 g/d) |
104 weeks |
N Analyzed | 147 | 143 | 143 | 150 |
Counts | 112 | 109 | 106 | 101 | |
Percentage | 76.2 | 76.2 | 74.1 | 67.3 |
Outcome: AE - Serious (SAE) Population: All Participants | |||||
---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA (1.2 g/d) | Pharm: 5-ASA (2.4 g/d) | Pharm: 5-ASA (4.8 g/d) |
104 weeks |
N Analyzed | 147 [1] | 143 | 143 | 150 |
Counts | 16 | 16 | 15 | 18 | |
Percentage | 10.9 | 11.19 | 10.49 | 12 | |
Footnotes | |||||
1. From NCT |
Outcome: AE - Sepsis (CD IV) Population: All Participants | |||||
---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA (1.2 g/d) | Pharm: 5-ASA (2.4 g/d) | Pharm: 5-ASA (4.8 g/d) |
104 weeks |
N Analyzed | 147 [1] | 143 | 143 | 150 |
Counts | 0 | 1 | 0 | 1 | |
Percentage | 0 | 0.7 | 0 | 0.67 | |
Footnotes | |||||
1. From NCT |
Outcome: AE - Major cardiac event (CD IV) Population: All Participants | |||||
---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA (1.2 g/d) | Pharm: 5-ASA (2.4 g/d) | Pharm: 5-ASA (4.8 g/d) |
104 weeks |
N Analyzed | 147 [1] | 143 | 143 | 150 |
Counts | 2 | 1 | 0 | 0 | |
Percentage | 1.36 | 0.70 | 0 | 0 | |
Footnotes | |||||
1. From NCT |
Outcome: AE - Infection requiring Abx (CD II) Population: All Participants | |||||
---|---|---|---|---|---|
Time Point | Measure | Placebo | Pharm: 5-ASA (1.2 g/d) | Pharm: 5-ASA (2.4 g/d) | Pharm: 5-ASA (4.8 g/d) |
104 weeks |
N Analyzed | 147 | 143 | 143 | 150 |
Counts | 17 | 14 | 12 | 8 | |
Percentage | 11.6 | 9.8 | 8.4 | 5.3 |
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 recurrence of diverticulitis were considered dropouts and assumed to be treatment failures for the intention-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 outcomes were reported. | |
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.