medwireNews: Results from an early-terminated clinical trial suggest dexamethasone is not a suitable nonoperative alternative to burr-hole drainage surgery for patients with symptomatic chronic subdural hematoma.
“Dexamethasone has the potential to block inflammatory changes in the subdural space, thereby impeding hematoma persistence and growth, and is administered to patients for this purpose in some institutions,” explain the investigators.
The open-label trial design, as published in The New England Journal of Medicine, required 420 study participants to attain a power of 90% to determine noninferiority of steroid therapy versus surgery with regard to functional outcomes on the modified Rankin scale.
However, study recruitment was stopped after the prespecified 3-month interim analysis raised safety and outcome concerns among the patients given dexamethasone.
Dexamethasone was associated with a higher rate of complications than surgery (59 vs 32%) and a greater likelihood of having more than one complication (59.1 vs 32.0%). The most common complications were infection (22.8 vs 19.2%), hyperglycemia (19.7 vs 4%), and delirium (15.7 vs 5.6%).
Moreover, 55.1% of patients given dexamethasone required surgery a median of 20 days after randomization, including 35 procedures before dexamethasone therapy was completed, and 10.4% required repeat surgery, compared with just 6.4% of the patients in the burr-hole drainage arm. The dexamethasone approach was also associated with a longer average hospital stay in the first 3 months of follow-up (12.0 vs 6.8 days).
The researchers report the results for the 252 patients who were recruited, 127 of whom were randomly assigned to receive a tapering course of dexamethasone for 19 days (8 mg every 12 hours on days 1–4, tapered by half every 3 days to 0.5 mg/day), while 125 patients instead underwent burr-hole drainage.
The participants were 74 years old, on average, and the majority (77.4%) were men. In all, 75.4% had experienced head trauma and 56.3% had used antithrombotic medication in the past.
Slightly more patients in the dexamethasone group had a bilateral subdural hematoma than did those receiving surgery (33.9 vs 26.4%) and at baseline only 37.8% of patients in the dexamethasone group scored between 0 (no symptoms) and 3 (moderate disability) on the 6-point modified Rankin scale versus 64.0% of patients in the surgery group, the investigators observe.
Overall, patients receiving dexamethasone were 45% less likely to have a better 3-month outcome than the burr-hole surgery patients according to the modified Rankin scale after adjustment for age, sex, Markwalder Grading score, baseline modified Rankin score, comorbidity, and use of antithrombotic therapy.
Specifically, at follow-up dexamethasone-treated patients were less likely than surgical controls to have no symptoms (17.5 vs 35.5%) or no clinically significant disability (26.2 vs 33.1%), and were more likely to have slight disability (20.6 vs 9.7%), moderate disability (18.3 vs 10.5%), or severe disability (2.4 vs 0.0%). Dexamethasone was also associated with a higher rate of death (6.3 vs 1.6%), although the likelihood of moderately severe disability was similar in the two arms (8.7 vs 9.7%).
The 95% confidence interval was 0.34 to 0.90, the lower limit of which did not meet or exceed the prespecified value for noninferiority of 0.9, report the researchers, led by Ishita Miah (Amphia Hospital, Breda, the Netherlands). However, they point out that “[f]rom the available outcomes when the trial was stopped, we could not affirm the noninferiority of dexamethasone on the basis of a prespecified margin.”
Findings for the secondary outcomes, as measured on the Markwalder Grading Scale of symptom severity and the Extended Glasgow Outcome Scale, “were generally supportive of the results of the primary analysis,” the team adds.
Nevertheless, Miah et al note that the study did not include patients with a Markwalder Grading scale of 3 and therefore the study conclusions “apply main to patients who are alert or drowsy with slight-to-moderate focal neurologic deficits.”
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