Evaluation of the Safety and Efficacy of Parecoxib in Patients With Subarachnoid Hemorrhage

NCT06579274 | Not Yet Recruiting Phase 2

• 1 other identifier: PAR-FNUSA-2024
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neurological Complication

Keywords

subarachnoidal hemorrhage; inflammation; NSAIDs

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

• Influence of parecoxib on outcome of patients with SAH

  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

  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)

  Six, eight and ten days, three and six months after the application of the first dose of the evaluated medicinal product /placebo.

• Mortality

  During the treatment and post treatment period of hospitalization, 90 days ± 7 days and 180 days ± 14 days

• Length of hospitalization in ICU

  3 months

Study Arms (2)

Active - Parecoxib

EXPERIMENTAL

Parecoxib 40 mg/100 ml will be injected into a peripheral or central venous catheter within 12 hours of the patient's inclusion in the study (from when informed consent is signed). Parecoxib 40 mg/100 ml is administered every 12 hours for 5 days. The maximum daily dose is 80 mg. In patients with moderate hepatic impairment (Child-Pugh score 7-9), parecoxib is started at 20 mg/50 mL and continued at this dose every 12 hours. The maximum daily dose is 40 mg. Participants will be monitored for six months for adverse events and changes in subjective status. In the event of adverse events, patients will be followed until resolution. After that, their participation in this clinical trial will be terminated. The total duration of the patient's participation in the clinical trial will be six months.

Drug: Parecoxib

Control - Placebo

PLACEBO COMPARATOR

A placebo is a substance administered to a participant as a comparison without any pharmacological effect. However, unlike conventional medicines, it does not contain any active ingredients. In this clinical trial, the placebo is an isotonic sodium chloride solution. The placebo is injected into a peripheral or central venous catheter within 12 hours of the patient's enrollment in the study (from when informed consent is signed). Placebo 100 mL per dose will continue to be administered every 12 hours for five days. Participants will be followed for six months for any adverse events and changes in subjective status. In the event of adverse effects, patients will be followed until resolution. After that, their participation in this clinical trial will be terminated. The total duration of the patient's participation in the clinical trial will be six months.

Drug: Placebo

Interventions

Parecoxib DRUG

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.

Active - Parecoxib

Placebo DRUG

Placebo intravenous injection can be administered quickly and directly into a vein or through an intravenous infusion set.

Control - Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• St. Anne's University Hospital Brno, Czech Republic: lead
• Masaryk University: collaborator
• CZECRIN - Czech Clinical Research Infrastructure Network: collaborator

Study Sites (1)

St. Anne's University Hospital Brno

Brno, Czech Republic, 602 00, Czechia

Location

MeSH Terms

Conditions

Inflammation

Interventions

parecoxib

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Peter Solar

  St. Anne´s University Hospital Brno

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lucie Tesárková

CONTACT

+420 543 185 174; lucie.tesarkova@fnusa.cz

Klara Kostelanska, PhD

CONTACT

+420 543 185 526; klara.kostelanska@fnusa.cz

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The clinical trial is planned as a multicenter, prospective, randomized, double-blind, placebo-controlled Phase II clinical trial, a so-called therapeutic exploratory study. This is an investigator-initiated, academic clinical trial to evaluate the safety and efficacy of parecoxib in hospitalized patients with spontaneous SAH.

Study Record Dates

• First Submitted: August 19, 2024
• First Posted: August 30, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 30, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)