Study Preview
Study Title and Description
Randomised clinical trial: mesalazine versus placebo in the prevention of diverticulitis recurrence. -B
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 | Randomised clinical trial: mesalazine versus placebo in the prevention of diverticulitis recurrence. -B |
Author | Kruis W., Kardalinos V., Eisenbach T., Lukas M., Vich T., Bunganic I., Pokrotnieks J., Derova J., Kondrackiene J., Safadi R., Tuculanu D., Tulassay Z., Banai J., Curtin A., Dorofeyev AE., Zakko SF., Ferreira N., Björck S., Diez Alonso MM., Mäkelä J., Talley NJ., Dilger K., Greinwald R., Mohrbacher R., Spiller R. |
Country | Cologne, Germany. |
Year | 2017 |
Numbers |
Pubmed ID: 28543263 |
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 | Pharm: 5-ASA (1.5 g/d) | ||
2 | Pharm: 5-ASA (3.0 g/d) | ||
3 | Placebo |
Question... Follow Up | Answer | Follow-up Answer | |
---|---|---|---|
Specific KQ | KQ 2b: Antibiotics (acute) | ||
KQ 2b: Antibiotics (acute) | |||
KQ 2b: Antibiotics (acute) | |||
KQ 2b: Antibiotics (acute) | |||
KQ 2b: Antibiotics (acute) | |||
Study Design | RCT | ||
RCT | |||
RCT | |||
RCT | |||
RCT | |||
Country | USA | ||
Germany | |||
USA | |||
Germany | |||
USA | |||
Germany | |||
USA | |||
Germany | |||
USA | |||
Germany | |||
Funder | Not reported (or unclear) | ||
Study name | SAG-57 | ||
Associated articles | |||
ClinicalTrials.gov identifier | NCT01038739 | ||
Start and end years of the Study | 2010 | ||
2013 | |||
Inclusion criteria | 30-80 yrs old. Prior diagnosis of left-sided uncomplicated acute diverticulitis confirmed by ultrasonography or CT with >=1 diverticulum in the left colon. Assessment of colonic wall thickening by ultrasonography or CT was required. Prior episode of left-sided uncomplicated diverticulitis was within the preceding 6 months and has been brought to clinical remission with antibiotics and/or dietary modification, documented by medical records. ≥3 of the following symptoms at the start of the most recent episode of diverticulitis: left lower quadrant pain, fever, altered bowel habit (diarrhoea, constipation, passage of mucus, or urgency) and systemic signs (nausea, lethargy). CRP > ULN at start of most recent attack. | ||
Exclusion criteria | Chronic IBD. Complicated diverticulitis (diverticulitis with associated abscess, fistula, obstruction or perforation), right-sided diverticulitis, previous colonic surgery, symptomatic organic disease of the GI tract, active colorectal cancer or history of colorectal cancer, active malignancy other than colorectal cancer or TX with anticancer drugs during the previous 5 yrs, haemorrhagic diathesis, active peptic ulcer disease, local intestinal infection, asthma without careful medical monitoring, abnormal hepatic function or liver cirrhosis, abnormal renal function, severe co-morbidity and/or immobility. Patients who received mesalazine-containing drugs, glucocorticosteroids, opioid analgesics, laxatives, antidiarrhoeals, immunosuppressants or non-steroidal anti-inflammatory drugs after the most recent episode. | ||
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 | Ultrasonography or CT with at least one diverticulum in the left colon. | ||
Note/Comment about Design (or overall study) |
Baseline Characteristics
Question | Pharm: 5-ASA (1.5 g/d) | Pharm: 5-ASA (3.0 g/d) | Placebo | Total | Comments | ||||
---|---|---|---|---|---|---|---|---|---|
Answer | Follow-up | Answer | Follow-up | Answer | Follow-up | Answer | Follow-up | ||
Participant race/ethnicity characteristics | Male | 30.9 | Male | 43.3 | Male | 44.1 | Male | 38.9 | |
Participant Age - Continuous data (in years) | Mean | 55.6 | Mean | 55.2 | Mean | 55.4 | Mean | 55.4 | |
SD | 10.4 | SD | 11.3 | SD | 10.3 | SD | 10.6 | ||
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) | 1 | 53.7 | 1 | 53.3 | 1 | 46.8 | 1 | 51.2 | |
2 | 29.3 | 2 | 26.7 | 2 | 36.9 | 2 | 31.2 | ||
>=3 | 5.7 | >=3 | 7.7 | >=3 | 9.0 | >=3 | 7.4 | ||
Other_1 (include definition in %) | 3: 11.4 | Other_1 (include definition in %) | 3: 12.2 | Other_1 (include definition in %) | 3: 7.2 | Other_1 (include definition in %) | 3: 10.2 | ||
History of (Prior) Complicated Diverticulitis | No data entered. | ||||||||
KQ 4: Time Since Last Episode of Diverticulitis | Mean | 93 days | Mean | 87 days | Mean | 88 days | Mean | 89 days | |
SD | 44 days | SD | 44 days | SD | 45 days | SD | 44 days | ||
Median | 78 days | Median | 76 days | Median | 79 days | Median | 78 days | ||
Range | 5-223 days | Range | 8-212 days | Range | 22-219 days | Range | 5-223 days | ||
Note/Comment about baseline characteristics | All information was retrieved from the supplementary table S1. | All information was retrieved from the supplementary table S1. | All information was retrieved from the supplementary table S1. | All information was retrieved from the supplementary table S1. | |||||
Number of Prior Episodes of Diverticulitis (continuous) | Mean | 93 days | Mean | 87 days | Mean | 88 days | Median | 78 days | |
SD | 44 days | SD | 44 days | SD | 45 days | Range | 5-223 days |
Results & Comparisons
Results Data
Outcome: Without recurrence Population: All Participants | Between-Arm Comparisons | |||||
---|---|---|---|---|---|---|
Time Point | Measure | Pharm: 5-ASA (1.5 g/d) | Pharm: 5-ASA (3.0 g/d) | Placebo | Comparison Measure | Pharm: 5-ASA (3.0 g/d) vs. Placebo |
48 weeks |
N Analyzed | 87 | 75 | 81 | 0.520 | |
Counts | 40 | 39 | 47 | |||
Percentage | 46 | 52 | 58 | |||
96 weeks |
N Analyzed | 58 | 51 | 52 | 0.110 | |
Counts | 4 | 5 | 12 | |||
Percentage | 6.9 | 9.8 | 23.1 |
Outcome: Without recurrence Population: 1 episode | ||||
---|---|---|---|---|
Time Point | Measure | Pharm: 5-ASA (1.5 g/d) | Pharm: 5-ASA (3.0 g/d) | Placebo |
48 weeks |
N Analyzed | 47 | 38 | 33 |
Counts | 26 | 21 | 20 | |
Percentage | 55.3 | 55.3 | 60.6 | |
96 weeks |
N Analyzed | |||
Counts | ||||
Percentage |
Outcome: Without recurrence Population: >1 episode | ||||
---|---|---|---|---|
Time Point | Measure | Pharm: 5-ASA (1.5 g/d) | Pharm: 5-ASA (3.0 g/d) | Placebo |
48 weeks |
N Analyzed | 40 | 37 | 48 |
Counts | 14 | 18 | 27 | |
Percentage | 35 | 48.6 | 56.3 | |
96 weeks |
N Analyzed | |||
Counts | ||||
Percentage |
Outcome: Recurrence of diverticulitis Population: All Participants | Between-Arm Comparisons | ||||||
---|---|---|---|---|---|---|---|
Time Point | Measure | Pharm: 5-ASA (1.5 g/d) | Pharm: 5-ASA (3.0 g/d) | Placebo | Comparison Measure | Pharm: 5-ASA (1.5 g/d) vs. Placebo | Pharm: 5-ASA (3.0 g/d) vs. Placebo |
48 weeks |
N Analyzed | 87 | 75 | 81 | 0.74 | 1.02 | |
Counts | 15 | 15 | 17 | 0.38 | 0.53 | ||
Percentage | 17.2 | 20 | 21 | 1.43 | 1.94 | ||
0.369 | 0.957 |
Outcome: Time to recurrence Population: All Participants | ||||
---|---|---|---|---|
Time Point | Measure | Pharm: 5-ASA (1.5 g/d) | Pharm: 5-ASA (3.0 g/d) | Placebo |
48 weeks |
SD | 134 | 125 | 162 |
Mean | 116 | 191 | 147 |
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 | Randomization was performed by means of a computer-generated randomization list, using randomly permuted blocks | |
Q15: Cochrane - Allocation concealment (selection bias): Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment | Low | The appearance and size of the placebo treatments were indistinguishable from the active mesalazine treatments and both patients and investigator were unaware of the treatment assignment. | |
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 | Missing outcome data was balanced in numbers, with similar reasons for missing data across both groups. Reasons for discontinuation are provided in Figure 1A and results section 3.1. | |
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 because patients 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.