A randomized, placebo-controlled, double-blind clinical trial evaluating the safety and efficacy of parecoxib in hospitalized patients with spontaneous subarachnoid hemorrhage

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fakultni Nemocnice U Sv Anny V Brne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

15 Dec 2025 → ongoing

Decision date (initial)

2025-02-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519436-17-00

ClinicalTrials.gov

NCT06579274

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary endpoint is the percentage of patients in the experimental and placebo groups whose clinical outcome according to the modified Rankin Scale (mRS) is graded as favorable (mRS 0-3) or unfavorable (mRS 4-6) 6 months after the first dose of the investigational drug/placebo.

Secondary objectives 17

1. To assess the effect of parecoxib/placebo on clinical outcome according to mRS at discharge and at 180 days ± 14 days after the first dose.
2. Assess the incidence of vasospasm (vasospasm confirmed on TCD/CT AG/MRI AG/DSA) during the treatment and post-treatment period during hospitalization.
3. To assess the incidence of late ischemic neurological deficit (DIND) during the treatment and post-treatment period of hospitalization.
4. Evaluate mortality during the treatment and post-treatment period during hospitalization and 90 days ± 7 days and 180 days ± 14 days from the first dose of the investigational drug/placebo.
5. To assess the incidence of acute hydrocephalus (EVD, LD) during the treatment and post-treatment period during hospitalization.
6. Assess the incidence of chronic hydrocephalus (need for V-P shunt implantation) during the treatment and post-treatment period during hospitalization and 90 days ± 7 days and 180 days ± 14 days after the first dose of the investigational drug/placebo.
7. Assess the length of hospitalization in the ICU, the total length of hospitalization.
8. To compare the incidence of febrile illness (body temperature above 38.0 °C) during the treatment and post-treatment period during hospitalization.
9. Laboratory evaluation of inflammatory markers (CRP, procalcitonin, leukocyte count) during the treatment and post-treatment period during hospitalization.
10. To assess the incidence of systemic inflammatory response (SIRS; assessed during the treatment and post-treatment period during hospitalization) meeting at least 2 parameters: heart rate > 90/min., leukocytosis > 12x109/l) or leukopenia < 9x109, respiratory frequency > 20/min. or PaCO2 < 32mm Hg (4,3kPa), body temperature < 36,0 °C or > 38,0 °C
11. Assess pain intensity according to VAS (daily in patients during hospitalization while conscious; highest VAS per day/average per day) during the treatment and post-treatment period during hospitalization.
12. To investigate and compare the levels 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 case of the need for external ventricular drainage every 2 days until the 10th day after implantation.
13. Assessment of the blood-brain barrier function every 2 days when cerebrospinal fluid drainage is required (the examination will be performed by collecting cerebrospinal fluid and blood and determining the albumin quotient, which is equal to the proportion of albumin in cerebrospinal fluid and albumin in serum).
14. Investigate and compare serum levels 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) á 2 days to day 10 after the first dose of parecoxib/placebo.
15. Assessment of quality of life (SF 36 score, Barthel Self-Efficacy Index), cognitive function (Montreal Cognitive Assessment - MoCA) and mood disturbance (Beck Depression Inventory II - BDI II; Beck Anxiety Inventory - BAI) in patients at discharge at 90 days ± 7 days and 180 days ± 14 days after the first dose of the investigational drug/placebo.
16. Percentage of patients in the experimental and placebo groups experiencing serious adverse events (SAEs) (assessed during hospitalization, at discharge, 90 days ± 7 days, and 180 days ± 14 days after the first dose of the investigational drug/placebo), supplemented by an assessment in each subgroup by source of bleeding.
17. Percentage of patients in the experimental and placebo groups experiencing elevations in blood creatine phosphokinase (CPK), elevations in blood lactate dehydrogenase (LDH), elevations in alanine transaminase (ALT), elevations in aspartate transaminase (AST), and elevations in blood urea > 5x ULN (assessed before administration of the investigational drug/placebo, during the treatment period, and post-treatment period during hospitalization); separate analysis for subgroups according to the source of bleeding.

Conditions and MedDRA coding

spontaneous subarachnoid hemorrhage

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Signed informed consent.
2. Age: 18-85 years
3. Weight > 50 kg.
4. 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.
5. 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 13

1. Symptoms of SAH without blood findings on the initial native CT scan of the brain.
2. History of congestive heart failure (NYHA II-IV).
3. History of coronary artery disease, peripheral arterial insufficiency.
4. Participation in another clinical trial (at least 5 half-lives apart before administration of the investigational medicinal product).
5. SAH due to a cause other than ruptured aneurysm, e.g. A-V malformation, traumatic SAH.
6. Pregnancy and breastfeeding (pregnancy test).
7. Known hypersensitivity to the components of the product.
8. History of allergic reaction to the active substance or to sulfonamides.
9. 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).
10. Severe hepatic insufficiency (serum albumin level <25 g /l or Child-Pugh score 10).
11. History of active peptic ulcer or gastrointestinal bleeding.
12. History of inflammatory bowel disease.
13. Systolic blood pressure ≥ 160 mmHg.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 18

1. 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).
2. Number of patients with vasospasms confirmed on TCD / CT AG / MR AG / DSA
3. Number of patients with delayed ischemic neurological deficit
4. Number of deaths
5. Length of hospitalization in ICU
6. Total length of hospitalization
7. Number of patients with acute hydrocephalus
8. Number of patients with chronic hydrocephalus with V-P shunt implantation
9. Number of patients with fever above 38 degrees Celsius
10. 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
11. 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.
12. 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
13. C-reactive protein (CRP), procalcitonin (PCT) and white blood cell count
14. This evaluation will compare the number of patients in the treatment and placebo arms who undergo cerebrospinal fluid drainage.
15. Evaluation of quality of life (SF-36 score)
16. Number of patients with inflamation based on source of bleeding
17. 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.
18. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fakultni Nemocnice U Sv Anny V Brne

Sponsor organisation

Fakultni Nemocnice U Sv Anny V Brne

Address

Pekarska 53, Stare Brno Stare Brno

City

Brno-Stred

Postcode

602 00

Country

Czechia

Scientific contact point

Organisation

Fakultni Nemocnice U Sv Anny V Brne

Contact name

MUDr. Peter Solár, Ph.D.

Public contact point

Organisation

Fakultni Nemocnice U Sv Anny V Brne

Contact name

Mgr. Klára Kostelanská, Ph.D.

Third parties 1

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 51 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications