A Clinical Trial About the Safety of Surgical Treatment in Severe Primary Pontine Hemorrhage

Surgery Clinical Trial

— STIPE  

Official title:

Safety of Surgical Treatment In Severe Primary Pontine Hemorrhage Evacuation (STIPE): a Multicentric, Randomized, Controlled, Open-label Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04647162
• Other study ID #: STIPE
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2022
• Est. completion date: November 2024

Study information

• Verified date: December 2023
• Source: West China Hospital
• Contact: Chao You, MD
• Phone: +86 028-85422488
• Email: youchao[@]vip.126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cerebrovascular Disorders
• Hemorrhage
• Pontine Hemorrhage
• Primary
• Surgery

Intervention

Procedure:
• hematoma evacuation by craniotomy
The intervention method of hematoma evacuation is under craniotomy.
• hematoma evacuation by stereotactic puncture
The intervention method of hematoma evacuation is under stereotactic puncture.
• hematoma evacuation by neuroendoscopy
The intervention method of hematoma evacuation is under neuroendoscopy.

Other:
• life support
The treatments in medical group includes life support, nutrition support, and rehabilitation therapy?

Locations

Country	Name	City	State
China	The Third Hospital of the People's Liberation Army	Baoji
China	The seventh medical center of the Army General Hospital	Beijing
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	Gaozhou Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine	Gaozhou	Guangdong
China	Guangdong Sanjiu Brain Hospital	Guangzhou	Guangdong
China	Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou
China	The First Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Mianyang Central Hospital	Mianyang	Sichuan
China	Affiliated Hospital of North Sichuan Medical College	Nanchong	Sichuan
China	General Hospital of the Eastern Theater	Nanjing	Jiangsu
China	Huashan Hospital of Fudan University	Shanghai
China	Shanghai No.10 hospital	Shanghai
China	Xuhui Hospital of Zhongshan Hospital affiliated to Fudan	Shanghai
China	The Second Affiliated Hospital of South China University of Technology	Shenzhen	Guangdong
China	University of Chinese Academy of Sciences Shenzhen Hospital	Shenzhen	Guangdong
China	Shanxi Bethune hospital	Taiyuan	Shanxi
China	The Second Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Zhuhai People's Hospital	Zhuhai	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
West China Hospital

Country where clinical trial is conducted

China, 

References & Publications (15)

Cao S, Zheng M, Hua Y, Chen G, Keep RF, Xi G. Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage. Stroke. 2016 Jun;47(6):1626-31. doi: 10.1161/STROKEAHA.116.013146. Epub 2016 Apr 28. — View Citation

Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, Fung GL, Goldstein JN, Macdonald RL, Mitchell PH, Scott PA, Selim MH, Woo D; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015 Jul;46(7):2032-60. doi: 10.1161/STR.0000000000000069. Epub 2015 May 28. — View Citation

Huang K, Ji Z, Sun L, Gao X, Lin S, Liu T, Xie S, Zhang Q, Xian W, Zhou S, Gu Y, Wu Y, Wang S, Lin Z, Pan S. Development and Validation of a Grading Scale for Primary Pontine Hemorrhage. Stroke. 2017 Jan;48(1):63-69. doi: 10.1161/STROKEAHA.116.015326. Epub 2016 Dec 8. — View Citation

Ichimura S, Bertalanffy H, Nakaya M, Mochizuki Y, Moriwaki G, Sakamoto R, Fukuchi M, Fujii K. Surgical Treatment for Primary Brainstem Hemorrhage to Improve Postoperative Functional Outcomes. World Neurosurg. 2018 Dec;120:e1289-e1294. doi: 10.1016/j.wneu.2018.09.055. Epub 2018 Sep 19. — View Citation

Indredavik B, Bakke F, Slordahl SA, Rokseth R, Haheim LL. Stroke unit treatment. 10-year follow-up. Stroke. 1999 Aug;30(8):1524-7. doi: 10.1161/01.str.30.8.1524. — View Citation

Lui TN, Fairholm DJ, Shu TF, Chang CN, Lee ST, Chen HR. Surgical treatment of spontaneous cerebellar hemorrhage. Surg Neurol. 1985 Jun;23(6):555-8. doi: 10.1016/0090-3019(85)90002-3. — View Citation

Mangiardi JR, Epstein FJ. Brainstem haematomas: review of the literature and presentation of five new cases. J Neurol Neurosurg Psychiatry. 1988 Jul;51(7):966-76. doi: 10.1136/jnnp.51.7.966. — View Citation

Morotti A, Jessel MJ, Brouwers HB, Falcone GJ, Schwab K, Ayres AM, Vashkevich A, Anderson CD, Viswanathan A, Greenberg SM, Gurol ME, Romero JM, Rosand J, Goldstein JN. CT Angiography Spot Sign, Hematoma Expansion, and Outcome in Primary Pontine Intracerebral Hemorrhage. Neurocrit Care. 2016 Aug;25(1):79-85. doi: 10.1007/s12028-016-0241-2. — View Citation

Murata Y, Yamaguchi S, Kajikawa H, Yamamura K, Sumioka S, Nakamura S. Relationship between the clinical manifestations, computed tomographic findings and the outcome in 80 patients with primary pontine hemorrhage. J Neurol Sci. 1999 Aug 15;167(2):107-11. doi: 10.1016/s0022-510x(99)00150-1. — View Citation

Parraga RG, Possatti LL, Alves RV, Ribas GC, Ture U, de Oliveira E. Microsurgical anatomy and internal architecture of the brainstem in 3D images: surgical considerations. J Neurosurg. 2016 May;124(5):1377-95. doi: 10.3171/2015.4.JNS132778. Epub 2015 Oct 30. — View Citation

Rohde V, Berns E, Rohde I, Gilsbach JM, Ryang YM. Experiences in the management of brainstem hematomas. Neurosurg Rev. 2007 Jul;30(3):219-23; discussion 223-4. doi: 10.1007/s10143-007-0081-9. Epub 2007 May 8. — View Citation

Steiner T, Al-Shahi Salman R, Beer R, Christensen H, Cordonnier C, Csiba L, Forsting M, Harnof S, Klijn CJ, Krieger D, Mendelow AD, Molina C, Montaner J, Overgaard K, Petersson J, Roine RO, Schmutzhard E, Schwerdtfeger K, Stapf C, Tatlisumak T, Thomas BM, Toni D, Unterberg A, Wagner M; European Stroke Organisation. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke. 2014 Oct;9(7):840-55. doi: 10.1111/ijs.12309. Epub 2014 Aug 24. — View Citation

Tao C, Li H, Wang J, You C. Predictors of Surgical Results in Patients with Primary Pontine Hemorrhage. Turk Neurosurg. 2016;26(1):77-83. doi: 10.5137/1019-5149.JTN.12634-14.1. — View Citation

Wilkinson DA, Keep RF, Hua Y, Xi G. Hematoma clearance as a therapeutic target in intracerebral hemorrhage: From macro to micro. J Cereb Blood Flow Metab. 2018 Apr;38(4):741-745. doi: 10.1177/0271678X17753590. Epub 2018 Jan 19. — View Citation

Ye Z, Huang X, Han Z, Shao B, Cheng J, Wang Z, Zhang Z, Xiao M. Three-year prognosis of first-ever primary pontine hemorrhage in a hospital-based registry. J Clin Neurosci. 2015 Jul;22(7):1133-8. doi: 10.1016/j.jocn.2014.12.024. Epub 2015 May 14. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Outcome Number 1: Rate of Mortality	Percentage of participants who died during the first 30 days after randomization.	30 days from randomization
Primary	Safety Outcome Number 2: Rate of Cerebritis, Meningitis, Bacterial Ventriculitis	Percentage of participants who had a bacterial brain infection (cerebritis, meningitis, ventriculitis) within 30 days of randomization.	30 days from randomization
Primary	Safety Outcome Number 3: Rate of Symptomatic Rebleeding	The difference in the rate of symptomatic rebleeding 72 hours post surgery.	72 hours post surgery
Secondary	the rate of hematoma clearance 3 days after surgery	the rate of hematoma clearance 3 days after surgery	3 days after surgery
Secondary	all-cause mortality at 365 days	all-cause mortality at 365 days	365 days after surgery
Secondary	neurological functional status of 30 days, 90 days, 180 days, and 365 days measured by Modified Rankin Scale (mRS), GCS and GOS.	neurological functional status of 30 days, 90 days, 180 days, and 365 days measured by Modified Rankin Scale (mRS), GCS and GOS.	30 days, 90 days, 180 days, and 365 days after surgery
Secondary	The Extended Glasgow Outcome Scale (EGOS) at 180 days and 365 days	The Extended Glasgow Outcome Scale (EGOS) at 180 days and 365 days	180 days and 365 days after surgery
Secondary	The 5-level EuroQol five dimensions questionnaire (EQ-5D) version (EQ-5D-5L) at 180 days and 365 days	The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The former descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The latter is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine.	180 days and 365 days after surgery
Secondary	the National Institutes of Health Stroke Scale (NIHSS) at 180 days and 365 days	the National Institutes of Health Stroke Scale (NIHSS) at 180 days and 365 days	180 days and 365 days after surgery