Clinical trial NCT05434065: Effects and Mechanisms of Celecoxib on Intracerebral Hemorrhage
Official title: Effects and Mechanisms of Celecoxib on Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Intracerebral Hemorrhage
Keywords: Intracerebral hemorrhage
Celecoxib
COX-2 inhibitor
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2022-06-27
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intracerebral hemorrhage
Primary purpose: TREATMENT

Brief summary: This trial is a phase IIa human clinical study, in which 60 patients with intracerebral hemorrhage (ICH) at basal ganglion or thalamus within 6 h after onset will be enrolled. Patients will be randomly assigned as treatment group or control group as 1:1 distribution. Early initiation of celecoxib within 6 h after ICH and treatment for 21 days will be performed. The safety will be evaluated by drug adverse effects. The efficacy will be assessed by hematoma expansion, brain edema, and 3-month modified Rankin scale.

Detailed description: A phase IIa human clinical trial will be performed to clarify the safety and efficacy of using usual dose of celecoxib (200 mg/day) for 21 days starting within 6 hours after onset of ICH. Totally 60 patients will be enrolled prospectively, and the case number was estimated by statistical methods for the percentage of participants with increased perihematomal edema volume shown in the previous clinical trial (Lee et al., 2013) (estimated by G-power software, settings as: exact test, one sample test, α = 0.05, power = 0.95). Patients will be randomly assigned as treatment group or control group as 1:1 distribution.

Intervention: Celecoxib 200 mg per dose, started within 6 h after onset, then one dose per day for 21 days in the treatment group. The low dose of Celecoxib will be used to minimize the side effect of Celecoxib. No trial medication will be given for the control group. Pregnancy will be excluded at enrollment and prevented throughout the treatment period in female cases at reproductive ages.

Evaluations:

1. Brain CT:

   1. Initial brain CT: for initial hematoma volume (length \* width \* height /2)
   2. Brain CT on day 2 for final hematoma volume and hematoma expansion
   3. Brain CT on day 7±1 for perihematomal edema and hematoma resolution
2. Neurological functions: NIHSS score, GCS score, modified Rankin scale (mRS) on day 1, 2, 7±2, 14±2, 21±2, and mRS at 3 months
3. Renal function (creatinine) on day 1, then once per week during day 2-7, day 8-14 and 15-21
4. Gastrointestinal bleeding evens within 21 days
5. Myocardial infarction evens within 21 days
6. Blood sampling on day 1, 7±2, and 21±2

Patient enrollment: If the patient's consciousness is not clear before the enrollment of this study, his (her) family can decide the enrollment for this patient. Once the patient regains his (her) consciousness, we will reconfirm with the patient about the enrollment of this study.

Data checks: The data recorded of this study will be double-checked for their accuracy and compared with predefined ranges to avoid typing error.

Plan for missing data: Missing data include those data which are reported as missing, unavailable, uninterpretable, or considered missing because of data inconsistency or out-of-range results. This study will try to minimize missing data by limiting the collection of data to essential information and minimizing the number of follow-up visits, develop a documentation of this study for the methods to screen the participants and the procedures to follow up, appropriate training for all personnel related to this study, and data will be reviewed as close to real-time as possible.

Statistical analysis plan: The continuous variables between Celecoxib group and control group will be compared using Mann-Whitney U test if these data are not with normal distribution, or t-test if these data are with normal distribution. Categorical data will be compared using Fisher's exact test.

Eligibility criteria: Inclusion Criteria:

* Acute ICH patients able to take the first dose within 6 hours after onset
* ICH location at basal ganglion or thalamus
* ICH volume \< 30 mL
* Normal renal function (creatinine \[Cr\] ≤ 1.3 mg/dL)
* No surgical indication
* Signed informed consent
* Consciousness clear or mild drowsiness
* Age 20-80 years old

Exclusion Criteria:

* Allergy to celecoxib or other non-steroid anti-inflammatory drugs (NSAIDs)
* Post-coronary artery bypass graft (CABG) within 14 days
* Previous myocardial infarction
* Previous peptic ulcer disease
* Abnormal renal function (Cr \> 1.3 mg/dL)
* Surgery for this ICH
* Pregnancy or under breast feeding (If the female case is not sure about pregnancy, pregnancy test will be performed)
* Premorbid mRS \> or = 3
* Previous ICH not at basal ganglia or thalamus
* Coagulation abnormality (abnormal PT/PTT), or taking anticoagulant or antiplatelet
* Abnormal liver function (ALT \> 3x upper limit)
* History of severe bleeding event, requiring admission or blood transfusion
* History of stenting or valve replacement, requiring long-term using antithrombotics

Primary outcomes:
measure: Hematoma expansion volume percentage
timeFrame: Day 2
measure: Perihematomal edema change volume percentage
timeFrame: Day 2, 7
measure: Percentage of participants with perihematomal edema volume change > 20%
timeFrame: Day 2, 7
Secondary outcomes:
measure: Hematoma expansion volume
timeFrame: Day 2
measure: Percentage of participants with hematoma expansion (33% relative or 12.5 mL absolute volume increase)
timeFrame: Day 2
measure: Perihematomal edema increase volume
timeFrame: Day 2, 7±1
measure: Hematoma and perihematomal edema expansion volume
timeFrame: Day 2, 7±1
measure: Hematoma and perihematomal edema expansion percentage
timeFrame: Day 2, 7±1
measure: Change in National Institutes of Health Stroke Scale (NIHSS)
timeFrame: Day 21±2
measure: Percentage of participants with adverse events (AEs)
timeFrame: Day 1-21
measure: modified Rankin scale (mRS) score
timeFrame: 3-month
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Natinal Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Shin-Joe Yeh, MD PhD
role: STUDY_CHAIR
References:
citation: Lee SH, Park HK, Ryu WS, Lee JS, Bae HJ, Han MK, Lee YS, Kwon HM, Kim CK, Park ES, Chung JW, Jung KH, Roh JK. Effects of celecoxib on hematoma and edema volumes in primary intracerebral hemorrhage: a multicenter randomized controlled trial. Eur J Neurol. 2013 Aug;20(8):1161-9. doi: 10.1111/ene.12140. Epub 2013 Mar 29.
citation: Dowlatshahi D, Demchuk AM, Flaherty ML, Ali M, Lyden PL, Smith EE; VISTA Collaboration. Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology. 2011 Apr 5;76(14):1238-44. doi: 10.1212/WNL.0b013e3182143317. Epub 2011 Feb 23.