Mego 2015.
| Methods | Study design: placebo‐controlled RCT, conducted at 6 cancer centres Duration of the study, recruitment: between January 2011 and December 2013 Follow‐up: not reported Country: Slovakia |
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| Participants | Inclusion criteria: age ≥ 18 years, histologically proven colorectal cancer, starting new line of chemotherapy based on irinotecan, ECOG performance status 0 or 1, life expectancy > 3 months; no psychological, familial, sociological or geographical condition potentially hampering compliance with study protocol and follow‐up schedule Exclusion criteria: impossible to take oral medication, active infection treated by antibiotic therapy, ileostomy, hypersensitivity to study drug, any concurrent malignancy other than non‐melanoma skin cancer, other cancer in past 5 years, serious concomitant systemic disorders or diseases incompatible with the study (at the discretion of investigator) Median age (range): 62 (45 to 75) versus 64 (42 to 81) years Male gender, n (%): 14 (60.9) versus 12 (52.2) Primary tumour site, n (%):
Karnofsky performance status, n (%):
Type of chemotherapy, n (%):
Biological therapy, n (%):
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| Interventions | Intervention (n = 23): probiotic formula Colon Dophilus™ (produced by Harmoniom International, Inc., Mirabel, Canada) 3*1 capsule per day orally for 12 weeks
"Each capsule contained 10*10⁹ CFU of bacteria. Each capsule contained 10 lyophilized probiotic strains including Bifidobacterium breve HA‐129 (25%), Bifidobacterium bifidum HA‐132 HA (20%), Bifidobacterium longum HA‐135 (14.5%), Lactobacillus rhamnosus HA‐111 (8%), Lactobacillus acidophilus HA‐122 (8%), Lactobacillus casei HA‐108 (8%), Lactobacillus plantarum HA‐119 (8%), Streptococcus thermopilus HA‐110 (6%), Lactobacillus brevis HA‐112 (2%), Bifidobacterium infantis HA‐116 (0.5%)" Control (n = 23): placebo Participants received full supportive care during irinotecan‐based chemotherapy including antidiarrhoeal drugs (loperamide, diphenoxylate/atropine) treatment, antiemetics, and analgesics when appropriate as a standard of care |
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| Outcomes | Grade 3 or 4 toxicity or SAE‐related toxicity according to NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE) Any grade gastrointestinal symptoms (enteritis, colitis, constipation, abdominal distension, bloating, flatulence, gastritis, dyspepsia, nausea, vomiting) according to NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE) |
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| Notes | Trial registration: NCT01410955 | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Participants were centrally randomised in ratio 1:1" "Participants were allocated to one of the treatment groups (probiotic or placebo) based on preformed randomization table" "Random allocation sequence was generated using random number table. Participants were stratified according to center, treatment with cetuximab, and irinotecan regimen (weekly versus every 2 to 3 weeks)" |
| Allocation concealment (selection bias) | Low risk | "After signing of informed consent, each patient received study number and investigator called to randomization center" "Investigator received the identification number of containers for randomised patient, and patient received corresponding containers" "Patients, investigators and statisticians were blinded to treatment allocation. All containers with probiotics/placebo looked the same and were sequentially numbered" |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "Patients, investigators and statisticians were blinded to treatment allocation. All containers with probiotics/placebo looked the same and were sequentially numbered" |
| Blinding of outcome assessment (detection bias) Subjective outcomes | Low risk | Participants were blinded |
| Blinding of outcome assessment (detection bias) Objective outcomes | Low risk | No information; however it is unlikely that assessment of objective outcomes (mortality) would have been influenced |
| Incomplete outcome data (attrition bias) Subjective outcomes | Low risk | No loss to follow‐up |
| Incomplete outcome data (attrition bias) Objective outcomes | Low risk | No loss to follow‐up |
| Selective reporting (reporting bias) | Low risk | All outcomes mentioned in the prospective trial register seem to have been presented (although it is not clear whether the 2‐year time frame was applied) |
| Other bias | Low risk | "The study was prematurely terminated due to slow accrual, when only 49 of 220 planned participants were accrued" |