de Jonghe 2014.
| Methods | Design: Multi‐centre randomised controlled trial Date of study: November 2008‐May 2012 Power calculation: performed, study adequately powered Frequency of outcomes assessment: Daily following inclusion until discharge; 3‐month follow‐up Inclusion criteria: Patients 65 years and older admitted for surgical treatment of hip fractures; enrolment within 24 hours of admission; individual willing to participate; medically able to receive study medication according to the protocol for the duration of the study Exclusion criteria: Delirium at enrolment; patients transferred from another hospital; if postoperative admission to the ICU or coronary care unit was anticipated; inability to speak or understand Dutch; concomitant use of melatonin |
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| Participants | Number in study: 452 Country: The Netherlands Setting: Teaching hospitals Age: Mean age 84.1 (SD 8.0) in intervention group, 83.4 (SD 7.5) in control group Sex: 53 (28.5%) male in intervention group, 62 (32.3%) of control group Co‐morbidity: Median Charlson Index 1.0 (IQR: 0.8‐2.0) in intervention group, 1.0 (IQR: 1.0‐2.0) in control group Dementia: Median MMSE 23 (IQR: 12‐28.8) in intervention group with 104 (55.9%) described as having cognitive impairment. Median MMSE 23 (IQR: 9.5‐28.0) in control group with 106 (55.2%) described as having cognitive impairment |
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| Interventions | Intervention: 3 mg of melatonin Control: Placebo |
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| Outcomes | 1. Incident delirium during the first eight days after initiation of the study medication using DSM‐IV and DOSS 2. Duration of delirium 3. 'Severe' delirium (defined as percentage of patients who received a total of ≥3mg haloperidol) 4. Length of admission 5. Use of psychotropic medications (reported as total dose rather than frequency of administration) 6. Cognitive outcomes at 3 months, using Charlson Index, IQCODE and MMSE 7. Functional outcomes at 3 months, using Katz ADL Index 8. In‐hospital mortality 9. Mortality at 3 months |
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| Notes | Funding source: Dutch National Program of Innovative Care for vulnerable older persons (a program operated by ZonMw, a Dutch institute that funds health research) Declarations of interest: None declared Delirium excluded at enrolment |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Low risk | Allocation blinded, randomisation list maintained by the trial pharmacist |
| Random sequence generation (selection bias) | Unclear risk | Randomisation was stratified by study centre, with fixed blocks of 10 patients within each stratum. Before the start of the study, an independent statistician generated a randomisation schedule and the trial pharmacist maintained the randomisation list Not described method of sequence generation |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Investigators, other staff members and patients remained blinded until after the last patient had completed the study and the follow‐up and data analyses had been completed |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | As above, blinded to allocation |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 452 were randomised of which 70 did not complete the study, generally balanced between the groups although rates of prevalent delirium different between groups. Complete reporting of reasons for withdrawals and missing data. |
| Selective reporting (reporting bias) | Low risk | Outcome data presented as per pre‐published protocol |
| Other bias | Low risk | No evidence of other bias |