Evaluation of the Safety and Efficacy of Parecoxib in Patients With Subarachnoid Hemorrhage
NCT Number: NCT06579274
Acronym: PARISAH
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Neurological Complication
Interventions: DRUG: Parecoxib|DRUG: Placebo
Sponsor: St. Anne's University Hospital Brno, Czech Republic
Collaborators: Masaryk University|CZECRIN - Czech Clinical Research Infrastructure Network
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 112
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, CARE_PROVIDER)|Primary Purpose: TREATMENT
Start Date: 2025-01-01
Completion Date: 2027-07-01
Locations: St. Anne's University Hospital Brno, Brno, Czech Republic, 602 00, Czechia

Summary:
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.

Primary Outcome Measures: Influence of parecoxib on outcome of patients with SAH, The primary outcome measure is the percentage of patients in the active and control groups whose outcome is categorized as favorable (mRS 0-3) or unfavorable (mRS 4-6) according to the modified Rankin Scale (mRS)., 180 days ± 14 days after first dose of parecoxib/placebo
Secondary Outcome Measures: Influence of parecoxib on outcome of patients with SAH, The secondary monitored parameter is the percentage of patients in the active and control groups whose outcome, according to the modified Rankin scale (mRS), is divided into favourable (mRS 0-3) or unfavourable (mRS 4-6)., 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, Number of patients with vasospasms confirmed on TCD / CT AG / MR AG / DSA, 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), Number of patients with delayed ischemic neurological deficit, Six, eight and ten days, three and six months after the application of the first dose of the evaluated medicinal product /placebo.|Mortality, Number of deaths, During the treatment and post treatment period of hospitalization, 90 days ± 7 days and 180 days ± 14 days|Length of hospitalization in ICU, Length of hospitalization in ICU, 3 months|Total length of hospitalization, Total length of hospitalization, 3 months|Occurrence of acute hydrocephalus, Number of patients with acute hydrocephalus, During the treatment and post treatment period of hospitalization|Occurrence of chronic hydrocephalus, Number of patients with chronic hydrocephalus with V-P shunt implantation, During the treatment and post treatment period of hospitalization, 90 days ± 7 days, 180 days ± 14 days|Occurrence of fevers, Number of patients with fever above 38 degrees Celsius, During the treatment and post treatment period of hospitalization|Occurrence of inflammation, Evaluation of the systemic inflammatory response (assessed daily during hospitalization) meeting at least 2 parameters:

* heart rate \> 90/min.
* leukocytosis \> 12x109/l) or leukopenia \< 9x109
* respiratory rate \> 20/min. or PaCO2 \< 32 mm Hg (4.3 kPa)
* body temperature \< 36.0 °C or \> 38.0 °C, During the treatment and post treatment period of hospitalization|Evaluation of pain according to Visual Analogue Scale, The comparison of the patients in the treatment and placebo arm with pain according to the Visual Analogue Scale, a numerical scale from 0 to 10 points, where increasing pain is indicated by a higher score., 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, Evaluation of prostaglandins (COX-2, PGH2, PGI2, PGE2, PGD2, PF2a, TXA2) and pro-inflammatory cytokines (TNF, IL-1, IL-4, IL-6, IL-8, IL-12) in the cerebrospinal fluid in the case of the below-mentioned external ventricular drainage after 2 days and in the serum regardless of the established cerebrospinal fluid drainage after two days to day 10 from initial symptoms, 0, 2, 4, 6, 8 and 10 days after implantation of drainage|Evaluatioon of laboratory markers of inflammatory response in peripheral blood, C-reactive protein (CRP), procalcitonin (PCT) and white blood cell count, Two, four, six, eight and ten days after the application of the first dose parecoxib/placebo|Evaluation of the functionality of the blood-cerebrospinal fluid barrier every 2 days if cerebrospinal fluid drainage is necessary., This evaluation will compare the number of patients in the treatment and placebo arms who undergo cerebrospinal fluid drainage., 0, 2, 4, 6, 8 and 10 days after implantation of drainage|Quality of life measured through questionnaires, Evaluation of quality of life (SF-36 score), Discharge from hospital, 90 days ± 7 days and 180 days ± 14 days after the application of the first dose parecoxib/placebo|Evaluation of the difference in efficacy parameters between subgroups according to the source of bleeding, Number of patients with inflamation based on source of bleeding, After discharge from hospital, six days after administration of the 1st dose of parecoxib/placebo|Serious adverse events, Percentage of patients in the experimental and placebo groups with the occurrence of serious adverse events (SAE) (assessed during hospitalization, at discharge, 3 and 6 months after the first dose) supplemented by evaluation in individual subgroups according to the source of bleeding., During hospitalization, at discharge, 90 days ± 7 days, 180 days ± 14 days after the first dose of parecoxib/placebo|Hepatotoxicity, Percentage of patients in the experimental and placebo groups with an increase in blood creatine phosphokinase (CPK), an increase in blood lactate dehydrogenase (LDH), an increase in alanine transaminase (ALT), an increase in aspartate transaminase (AST), and an increase in blood urea level \> 5x ULN; separate analysis for subgroups by source of bleeding., Before the 1st dose of parecoxib/placebo, 1., 3. and 5. day of treatment and 10. day of hospitalization