gms | German Medical Science

Objective: The chronic subdural hematoma (cSDH) shows an increasing incidence in an aging population over the last 20 years while inacceptable recurrence rates of up to 30% persist. The recurrence rate of cSDH seems to be related to the insufficient neoangiogenesis in the parietal membrane which is mediated via VEGF. This is found to be elevated in the hematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclooxygenase-2. With this investigator initiated trial (IIT) it was thought to diminish the recurrence rate of operated cSDH by administering a selective cyclooxygenase-2-inhibitor (Celecoxib) over a 4 weeks time postoperatively in comparison to a control group.

Method: The thesis of riskreduction of cSDH recurrence in cyclooxygenase-2-inhibited patients was to be determined in a prospective, randomized, two armed, open phase II/III study with inclusion of 180 patients over a two years time period in 4 German university hospitals. The data were to be analysed by a confirmatory comparison (fisher exact test on a significance level of alpha 0.05 (two-sided))

Results: After screening of 246 patients from January 2009 to April 2010 the study had to be terminated premature as only 23 patients (9,3%) could be enrolled because of on-going NSAR-treatment or contraindication to Celecoxib medication. In the study population 13 patients were treated in the control group (female 6, male 7, average age 66,8 years, 1 AE/SAE needing 1 re-operation because of progressive cSDH (7,7%)), 10 patients were treated in the treatment group (female 1, male 9, average age 64,7, 5 AE/SAE needing 2 re-operations because of 1 progressive cSDH and 1 wound infection (20%)). Significance levels are obsolete because of insufficient patient numbers.

Conclusions: The theoretical advantage of cyclooxygenase-2-inhibition in the recurrent cSDH could not be transferred into the treatment of German cSDH patients as 66,6% of the patients showed strict contraindications for Celecoxib. Furthermore 55% of the patients were already treated with any kind of COX-2-inhibiton and even these patients develop chronic subdural hematoma. Thus, although conceptually appealing an anti-angiogenic therapy of COX-2 inhibitors for cSDH cannot be realized in this patient population due to the high prevalence of comorbidities excluding the administration of COX2 inhibitors.