PARECOXIB for Spontaneous subarachnoid hemorrhage

Inclusion criteria

• {"criterion_text":"- Signed informed consent.\n- Age: 18-85 years\n- Weight > 50 kg.\n- Spontaneous SAH diagnosed on native brain CT within 48 hours of first symptoms due to rupture of a bulge in one of the cerebral arteries confirmed by on DSA or CT angiography (Fisher grade 1 to 4) OR Spontaneous SAH without source by CT AG, DSA or MRI with Fisher grade 3 and 4.\n- For women capable of becoming pregnant (see definition from CTFG contraceptive guidelines): use of the following highly reliable contraceptive method within 3 months of study completion: adherence to sexual abstinence or progesterone-containing contraceptives with ovulation inhibition (oral administration, injection) or intrauterine device non-hormonal or hormonal or bilateral tubal occlusion or partner vasectomy. Men: adherence to sexual abstinence or use of an adequate contraceptive method (i.e., condom) in the event of sexual intercourse within 3 months of study completion."}

Exclusion criteria

• {"criterion_text":"- Symptoms of SAH without blood findings on the initial native CT scan of the brain.\n- Severe hepatic insufficiency (serum albumin level <25 g /l or Child-Pugh score 10).\n- History of active peptic ulcer or gastrointestinal bleeding.\n- History of inflammatory bowel disease.\n- Systolic blood pressure ≥ 160 mmHg.\n- History of congestive heart failure (NYHA II-IV).\n- History of coronary artery disease, peripheral arterial insufficiency.\n- Participation in another clinical trial (at least 5 half-lives apart before administration of the investigational medicinal product).\n- SAH due to a cause other than ruptured aneurysm, e.g. A-V malformation, traumatic SAH.\n- Pregnancy and breastfeeding (pregnancy test).\n- Known hypersensitivity to the components of the product.\n- History of allergic reaction to the active substance or to sulfonamides.\n- Concomitant treatment with another non-steroidal anti-inflammatory drug, aspirin or corticosteroids (at least 5 half-lives apart before administration of the investigational medicinal product)."}

Primary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Clinical outcome according to the modified Rankin Scale (mRS) graded as favorable (mRS 0-3) or unfavorable (mRS 4-6), assessed 6 months after the first dose of the investigational drug/placebo."}

Secondary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"mRS outcome at discharge and at 180 days ± 14 days after first dose (as per secondary objectives)."}
• {"endpoint_text":"- Number of patients with vasospasms confirmed on TCD / CT AG / MR AG / DSA","definition_or_measurement_approach":"Incidence of vasospasm confirmed by transcranial Doppler (TCD), CT angiography, MR angiography or digital subtraction angiography (DSA) during treatment and post-treatment hospitalization period."}
• {"endpoint_text":"- Number of patients with delayed ischemic neurological deficit","definition_or_measurement_approach":"Incidence of delayed ischemic neurological deficit (DIND) during treatment and post-treatment hospitalization period."}
• {"endpoint_text":"- Number of deaths","definition_or_measurement_approach":"Mortality assessed during treatment and post-treatment hospitalization period and at 90 days ± 7 days and 180 days ± 14 days from first dose."}
• {"endpoint_text":"- Length of hospitalization in ICU","definition_or_measurement_approach":"Duration of ICU stay during index hospitalization."}
• {"endpoint_text":"- Total length of hospitalization","definition_or_measurement_approach":"Total duration of hospital stay during index hospitalization."}
• {"endpoint_text":"- Number of patients with acute hydrocephalus","definition_or_measurement_approach":"Incidence of acute hydrocephalus (EVD, LD) during treatment and post-treatment hospitalization period."}
• {"endpoint_text":"- Number of patients with chronic hydrocephalus with V-P shunt implantation","definition_or_measurement_approach":"Incidence of chronic hydrocephalus requiring V-P shunt implantation during hospitalization and at follow-up (90 days ±7, 180 days ±14)."}
• {"endpoint_text":"- Number of patients with fever above 38 degrees Celsius","definition_or_measurement_approach":"Incidence of febrile illness (body temperature > 38.0 °C) during treatment and post-treatment hospitalization period."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Daily assessment for SIRS during hospitalization; SIRS defined as meeting at least two listed physiological/laboratory criteria."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Pain intensity measured daily during hospitalization using VAS (0-10); highest VAS per day and average per day recorded."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Laboratory assessment of specified prostaglandins and cytokines in CSF (if EVD placed, every 2 days until day 10) and in serum from day 2 to day 10 after first dose."}
• {"endpoint_text":"- C-reactive protein (CRP), procalcitonin (PCT) and white blood cell count","definition_or_measurement_approach":"Laboratory evaluation of inflammatory markers (CRP, PCT, WBC) during treatment and post-treatment hospitalization period."}
• {"endpoint_text":"- This evaluation will compare the number of patients in the treatment and placebo arms who undergo cerebrospinal fluid drainage.","definition_or_measurement_approach":"Comparison of frequency of CSF drainage procedures between arms."}
• {"endpoint_text":"- Evaluation of quality of life (SF-36 score)","definition_or_measurement_approach":"Quality of life assessed using SF-36 at discharge, 90 days ±7, and 180 days ±14 after first dose."}
• {"endpoint_text":"- Number of patients with inflamation based on source of bleeding","definition_or_measurement_approach":"Incidence of inflammation stratified by bleeding source."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Proportion of patients with SAEs assessed during hospitalization, at discharge, 3 months and 6 months after first dose, with subgroup analyses by bleeding source."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Proportion of patients with laboratory abnormalities (CPK, LDH, ALT, AST, blood urea >5xULN) measured before administration, during treatment and post-treatment; subgroup analysis by bleeding source."}

Czechia

Earliest CTIS Part Ii Submission Date

28-01-2025

Latest Decision Or Authorization Date

13-02-2026

Processing Time Days

381

Number Of Sites

3

Number Of Participants

112

Primary sponsor

Full Name

Fakultni Nemocnice U Sv Anny V Brne

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Czechia

Third parties

• {"country":"Czechia","full_name":"Masarykova Univerzita","duties_or_roles":"8","organisation_type":"Educational Institution"}