Evaluation of the Safety and Efficacy of Parecoxib in Patients With Subarachnoid Hemorrhage
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An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Parecoxib, Placebo.
- Who it may be relevant to
- Registry conditions: Neurological Complication. Basic parameters: 18 years — 85 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Czechia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Randomized, Placebo-controlled, Double-blind Clinical Trial Evaluating the Safety and Efficacy of Parecoxib in Hospitalized Patients With Spontaneous Subarachnoid Hemorrhage
Overview
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.
Detailed description
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.
Interventions
- Drug Parecoxib
Parecoxib (Dynastat) 40 mg solution for injection is for intravenous administration. Parecoxib may be given as an intravenous injection for 30 minutes directly into a vein or through an intravenous infusion set. - Drug Placebo
Placebo intravenous injection can be administered quickly and directly into a vein or through an intravenous infusion set.
Primary outcome measures
- Influence of parecoxib on outcome of patients with SAH [Time frame: 180 days ± 14 days after first dose of parecoxib/placebo]
Secondary outcome measures (12)
- Influence of parecoxib on outcome of patients with SAH [Time frame: Discharge from hospital and 90 days ± 7 days after first dose of parecoxib/placebo]
- Occurrence of symptomatic vasospasms (vasospasms confirmed on TCD / CT AG / MR AG / DSA [Time frame: Six, eight and ten days after the application of the first dose of the evaluated medicinal product /placebo.]
- Incidence of delayed ischemic neurological deficit (DIND) [Time frame: Six, eight and ten days, three and six months after the application of the first dose of the evaluated medicinal product /placebo.]
- Mortality [Time frame: During the treatment and post treatment period of hospitalization, 90 days ± 7 days and 180 days ± 14 days]
- Length of hospitalization in ICU [Time frame: 3 months]
- Total length of hospitalization [Time frame: 3 months]
- Occurrence of acute hydrocephalus [Time frame: During the treatment and post treatment period of hospitalization]
- Occurrence of chronic hydrocephalus [Time frame: During the treatment and post treatment period of hospitalization, 90 days ± 7 days, 180 days ± 14 days]
- Occurrence of fevers [Time frame: During the treatment and post treatment period of hospitalization]
- Occurrence of inflammation [Time frame: During the treatment and post treatment period of hospitalization]
- Evaluation of pain according to Visual Analogue Scale [Time frame: During the treatment and post treatment period of hospitalization, discharge from hospital, 90 days ± 7 days and 180 days ± 14 days after first dose of parecoxib/placebo]
- Evaluation of prostaglandins and pro-inflammatory cytokines in the cerebrospinal fluid in the case of the below-mentioned external ventricular drainage after 2 days and in the serum [Time frame: 0, 2, 4, 6, 8 and 10 days after implantation of drainage]
Eligibility criteria
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).
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Double blind
- Primary purpose
- Treatment
Study locations
Czechia · 1 center
- St. Anne's University Hospital Brno — Brno
Identifiers
NCT: NCT06579274 · PAR-FNUSA-2024