Because of the important role of inflammation in the pathophysiology of SAH, it was hypothesized that its pharmacological manipulation might improve the prognosis of patients. In recent years, the effects of several groups of anti-inflammatory drugs on the development of complications after SAH have been described. Initially promising, glucocorticoids, thought to reduce cerebrovascular inflammation, brain swelling, and headache, failed in clinical trials. Studies have not provided clear evidence of the beneficial effects of these drugs in patients after SAH. Therefore, the administration of glucocorticoids is not currently part of the recommended practice. In addition, glucocorticoid treatment is associated with adverse effects that worsen outcomes, including hyperglycemia, infection, and the risk of gastrointestinal bleeding.

Spontaneous subarachnoid hemorrhage (SAH) is a specific type of hemorrhagic stroke with a worldwide incidence ranging from 0.5 to 28 per 100,000 population, with large regional variations. Despite improvements in diagnosis, treatment and care, SAH remains a disease with high mortality and morbidity. According to the literature, one third of patients die within the first few days after SAH, and most survivors have cognitive impairment or long-term disability. The overall clinical outcome depends on the severity of early brain injury (EBI), cerebral edema, hydrocephalus, development of delayed ischemic neurological deficit (DIND), epileptic seizures, and other complications. The pathophysiological cascades responsible for the development of these complications remain poorly understood. However, numerous studies support the important role of aseptic cerebrovascular inflammation induced by blood and blood breakdown products in the subarachnoid space after SAH. The increased interest in the development of cerebrovascular inflammation after SAH is confirmed by the increasing number of clinical and experimental studies devoted to this topic. Cerebrovascular aseptic inflammation as a potential treatment target is also mentioned in current guidelines for the management of patients after SAH.

The results of experimental studies formed the basis for the clinical evaluation of the effects of NSAIDs after SAH. The effects of several commonly used NSAIDs, particularly dexketoprofen, ibuprofen, diclofenac, indomethacin, or dipyrone, have been evaluated in prospective and retrospective clinical trials over the past decade. In addition to reducing pro-inflammatory markers such as IL6, lowering body temperature and platelet aggregation, the administration of NSAIDs has been associated with reduced mortality and improved clinical outcomes. Despite the beneficial effects of some NSAIDs, more robust studies are still lacking, except for one study that evaluated the effect of meloxicam in patients after SAH. This study was a randomized, double-blind, placebo-controlled trial. It showed a trend towards a better outcome with a lower incidence of vasospasm or mortality in patients after SAH.

Despite encouraging experimental results, no clinical trials have yet evaluated the anti-inflammatory and other potentially beneficial effects of cyclooxygenase-2 (COX-2) inhibitors. COX-2 inhibitors, or coxibs, belong to the group of NSAIDs that selectively inhibit the COX-2 enzyme, which is responsible for developing inflammation and pain. A planned clinical study will evaluate the effects of parecoxib, a specific COX-2 inhibitor in the NSAIDs group, on overall clinical outcome and development of complications in patients following spontaneous SAH.

Inclusion Criteria:

• Signed informed consent
• Age: 18-85 years
• Weight> 50 kg
• Spontaneous SAH diagnosed on a native CT brain max. 48 hours after the first symptoms
• Spontaneous SAH caused by rupture of the cerebral aneurysm confirmed on DSA or CT angiography (Fisher grade 1 to 4) OR Spontaneous SAH without a source on CT AG, DSA or MRI with Fisher grade 3 and 4
• For women capable of becoming pregnant (see definitions from the CTFG guideline for contraception): use of the following highly reliable contraceptive method within 3 months after the end of the study: adherence to sexual abstinence or contraception containing progesterone with inhibition of ovulation (oral administration, injection) or non-hormonal intrauterine device or hormonal or bilateral tubal occlusion or partner vasectomy. Males: adherence to sexual abstinence or use of an adequate contraceptive method (i.e. condom) in case of sexual intercourse within 3 months after the end of the study.

Exclusion Criteria:

• Symptoms of SAH without the finding of blood on the initial native CT scan of the brain
• SAH from a cause other than a ruptured aneurysm, e.g. A-V malformation, traumatic SAH
• Pregnancy and breastfeeding (pregnancy test)
• Known hypersensitivity to the components of the product
• Allergic reaction to the active substance or sulfonamides in the anamnesis
• Concomitant treatment with other non-steroidal anti-inflammatory drugs, aspirin or corticosteroids (at least five half-lives before administration of the medicinal product under investigation)
• Severe hepatic insufficiency (serum albumin level <25 g/l or Child-Pugh score less than 10).
• Active peptic ulcer or bleeding from the gastrointestinal tract in the anamnesis
• Inflammatory bowel disease in the anamnesis
• Congestive heart failure (NYHA II-IV) in history.
• Proven ischemic heart disease, peripheral arterial insufficiency.
• Participation in another clinical study (a gap of at least five half-lives before administration of the medicinal product under investigation).

This clinical trial will be double-blind, with participants and investigators unaware of which treatment arm they have been assigned to.

Blinding will be done automatically by code assignment via the RedCap electronic database. Only the investigating physician can assign the code to the patient and unblind the patient at the same time. The data manager will have a list of codes for possible unblinding.

Unblinding the patient for any reason is considered a protocol deviation. The reason for unblinding will be described in the source documentation and recorded in the eCRF. In an emergency, the investigator may perform unblinding himself according to ICH GCP E6(R2) paragraph 4.7.