Clinical trial NCT04647162: A Clinical Trial About the Safety of Surgical Treatment in Severe Primary Pontine Hemorrhage
Official title: Safety of Surgical Treatment In Severe Primary Pontine Hemorrhage Evacuation (STIPE): a Multicentric, Randomized, Controlled, Open-label Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cerebrovascular Disorders
Pontine Hemorrhage
Primary
Surgery
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2020-11-30
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A sample size of 60 would be required to demonstrate a significant level of 5% (two-sided) with 80% power. Considering the 6% missing rate during follow-up, the total sample size was 64 cases with 16 and 48 cases in MT and HE group, respectively.
Primary purpose: TREATMENT

Brief summary: Primary pontine hemorrhage (PPH) is not common but is the most catastrophic subtype of intracerebral hemorrhage, with acute mortality between 30% and 60%. For severe PPH, defined as Glasgow Coma score (GCS) \<8 and hematoma volume≥5ml, the mortality rate is as high as 80-100%. Guidelines from the American Heart Association and European Stroke Organization do not make definite specifications. More than a century after Finkelnburg first explored the brainstem for hematoma, however, plenty of researches have shown surgery can save lives and improve the prognosis for selective patients and can be an effective and safe treatment. This study is proposed to validate the safety of surgical treatment in severe primary pontine hemorrhage.

Detailed description: The study is being conducted from Jan 2022 to Nov 2024 in 20 neurosurgical units. This STIPE trial is an investigator-initiated, parallel (3:1 to surgical HE or MT), multi-centre, randomized controlled open-label trial following the Consolidated Standards of Reporting Trials (CONSORT) guidelines and will be conducted from Jan 2022 to Nov 2024 in 20 Tertiary hospitals in China. The flow chart of the clinical trial is presented in Figure 1. Neurosurgeons involved in the study are senior investigators with good clinical experience in sPPH management. Moreover, all investigators are well trained centrally according to the requirements.

Eligibility criteria: Inclusion Criteria:

1. Clinical diagnosis of PPH: patients have acute hemorrhage mainly in pons with a definite history of hypertension.
2. GCS 5\~7 and HV≥5ml on admission (the HV in intraventricular system being excluded).
3. Family members consenting to randomize and signing informed consent form (ICF).
4. Time from onset to admission less than 24 hours.
5. Age:18 years or older.

Exclusion Criteria:

1. Structural lesions such as brainstem cavernous malformation, arteriovenous malformation, aneurysm, tumor apoplexy.
2. GCS≥8 and HV\<5ml.
3. Time from onset to admission over 24 hours.
4. Patients with platelet count \< 100,000, International Normalized Ratio (INR)\> 1.4, or an elevated prothrombin time (PT) and activated partial thromboplastin time (APTT).
5. Multiple ICH.
6. Accompanying hydrocephalus that requires surgical management
7. Irreversible brainstem failure (bilateral fixed, dilated pupils and extensor motor posturing, GCS≤4).
8. A previous history of ICH.
9. Any serious concurrent illness that would interfere with the safety assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease.
10. Pregnant patients.
11. Patients' family members refuse HE.
12. Any other condition that the investigator believes would present a significant hazard to the subject if the investigational therapy were initiated.
13. Participating in another simultaneous trial of ICH treatment.

Primary outcomes:
measure: Safety Outcome Number 1: Rate of Mortality
timeFrame: 30 days from randomization
measure: Safety Outcome Number 2: Rate of Cerebritis, Meningitis, Bacterial Ventriculitis
timeFrame: 30 days from randomization
measure: Safety Outcome Number 3: Rate of Symptomatic Rebleeding
timeFrame: 72 hours post surgery
Secondary outcomes:
measure: the rate of hematoma clearance 3 days after surgery
timeFrame: 3 days after surgery
measure: all-cause mortality at 365 days
timeFrame: 365 days after surgery
measure: neurological functional status of 30 days, 90 days, 180 days, and 365 days measured by Modified Rankin Scale (mRS), GCS and GOS.
timeFrame: 30 days, 90 days, 180 days, and 365 days after surgery
measure: The Extended Glasgow Outcome Scale (EGOS) at 180 days and 365 days
timeFrame: 180 days and 365 days after surgery
measure: The 5-level EuroQol five dimensions questionnaire (EQ-5D) version (EQ-5D-5L) at 180 days and 365 days
timeFrame: 180 days and 365 days after surgery
measure: the National Institutes of Health Stroke Scale (NIHSS) at 180 days and 365 days
timeFrame: 180 days and 365 days after surgery
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Gaozhou
country: China
facility: Gaozhou Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Sanjiu Brain Hospital
state: Guangdong
city: Shenzhen
country: China
facility: University of Chinese Academy of Sciences Shenzhen Hospital
state: Guangdong
city: Shenzhen
country: China
facility: The Second Affiliated Hospital of South China University of Technology
state: Guangdong
city: Zhuhai
country: China
facility: Zhuhai People's Hospital
state: Guangdong
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: The Second Affiliated Hospital of Zhengzhou University
state: Henan
city: Nanjing
country: China
facility: General Hospital of the Eastern Theater
state: Jiangsu
city: Taiyuan
country: China
facility: Shanxi Bethune hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Nanchong
country: China
facility: Affiliated Hospital of North Sichuan Medical College
state: Sichuan
city: Baoji
country: China
facility: The Third Hospital of the People's Liberation Army
city: Beijing
country: China
facility: The seventh medical center of the Army General Hospital
city: Hangzhou
country: China
facility: Second Affiliated Hospital of Zhejiang University School of Medicine
city: Shanghai
country: China
facility: Huashan Hospital of Fudan University
city: Shanghai
country: China
facility: Shanghai No.10 hospital
city: Shanghai
country: China
facility: Xuhui Hospital of Zhongshan Hospital affiliated to Fudan
Study officials:
affiliation: West China Hospital
name: Chao You, MD
role: PRINCIPAL_INVESTIGATOR
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