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

NCT04647162 | Unknown DMC

• 1 other identifier: STIPE
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 20

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.

Conditions

Cerebrovascular Disorders; Pontine Hemorrhage; Primary; Surgery

Outcome Measures

Primary Outcomes (3)

• Safety Outcome Number 1: Rate of Mortality

  Percentage of participants who died during the first 30 days after randomization.

  30 days from randomization

• 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

• 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 Outcomes (6)

• the rate of hematoma clearance 3 days after surgery

  3 days after surgery

• all-cause mortality at 365 days

  365 days after surgery

• 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

• The Extended Glasgow Outcome Scale (EGOS) at 180 days and 365 days

  180 days and 365 days after surgery

• The 5-level EuroQol five dimensions questionnaire (EQ-5D) version (EQ-5D-5L) at 180 days and 365 days

  180 days and 365 days after surgery

Study Arms (2)

medical group

ACTIVE COMPARATOR

Patients receive only medical treatment including active life support, nutritional support, homeostasis maintenance of the internal environment, and other symptomatic treatment.

Other: life support

surgical group

EXPERIMENTAL

Patients receive intervention such as the evacuation of hematoma under craniotomy or by stereotactic puncture or neuroendoscopy.

Procedure: hematoma evacuation by craniotomy; Procedure: hematoma evacuation by stereotactic puncture; Procedure: hematoma evacuation by neuroendoscopy

Interventions

hematoma evacuation by craniotomy PROCEDURE

The intervention method of hematoma evacuation is under craniotomy.

surgical group

hematoma evacuation by stereotactic puncture PROCEDURE

The intervention method of hematoma evacuation is under stereotactic puncture.

surgical group

hematoma evacuation by neuroendoscopy PROCEDURE

The intervention method of hematoma evacuation is under neuroendoscopy.

surgical group

life support OTHER

The treatments in medical group includes life support, nutrition support, and rehabilitation therapy。

medical group

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: based on the identity card
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (20)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

RECRUITING

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

RECRUITING

Gaozhou Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine

Gaozhou, Guangdong, China

RECRUITING

Guangdong Sanjiu Brain Hospital

Guangzhou, Guangdong, China

RECRUITING

University of Chinese Academy of Sciences Shenzhen Hospital

Shenzhen, Guangdong, 518000, China

RECRUITING

The Second Affiliated Hospital of South China University of Technology

Shenzhen, Guangdong, China

RECRUITING

Zhuhai People's Hospital

Zhuhai, Guangdong, China

RECRUITING

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

RECRUITING

The Second Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

RECRUITING

General Hospital of the Eastern Theater

Nanjing, Jiangsu, China

RECRUITING

Shanxi Bethune hospital

Taiyuan, Shanxi, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, China

RECRUITING

Mianyang Central Hospital

Mianyang, Sichuan, China

RECRUITING

Affiliated Hospital of North Sichuan Medical College

Nanchong, Sichuan, China

RECRUITING

The Third Hospital of the People's Liberation Army

Baoji, China

RECRUITING

The seventh medical center of the Army General Hospital

Beijing, China

RECRUITING

Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, China

RECRUITING

Huashan Hospital of Fudan University

Shanghai, China

RECRUITING

Shanghai No.10 hospital

Shanghai, China

RECRUITING

Xuhui Hospital of Zhongshan Hospital affiliated to Fudan

Shanghai, China

RECRUITING

Related Publications (16)

• 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.

  PMID: 26759226 BACKGROUND

• 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.

  PMID: 25982189 BACKGROUND

• 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.

  PMID: 26768872 BACKGROUND

• 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.

  PMID: 27932606 BACKGROUND

• 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.

  PMID: 10436094 BACKGROUND

• 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.

  PMID: 26022637 BACKGROUND

• 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.

  PMID: 25156220 BACKGROUND

• 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.

  PMID: 3992454 BACKGROUND

• 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.

  PMID: 30244074 BACKGROUND

• 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.

  PMID: 3060565 BACKGROUND

• 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.

  PMID: 17486379 BACKGROUND

• 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.

  PMID: 10521548 BACKGROUND

• 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.

  PMID: 27125525 BACKGROUND

• 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.

  PMID: 29350086 BACKGROUND

• 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.

  PMID: 26517774 BACKGROUND

• He Q, Wang J, Ma L, Li H, Tao C, You C. Safety of surgical Treatment In severe primary Pontine haemorrhage Evacuation (STIPE): study protocol for a multi-centre, randomised, controlled, open-label trial. BMJ Open. 2022 Aug 23;12(8):e062233. doi: 10.1136/bmjopen-2022-062233.

  PMID: 35998952 DERIVED

MeSH Terms

Conditions

Cerebrovascular Disorders

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Chao You, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao You, MD

CONTACT

+86 028-85422488; youchao@vip.126.com

Qiang He, MD

CONTACT

+86 15099189463; heqiang629@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: former director of the department of neurosurgery, West China Hospital

Model Details: 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.

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 30, 2020
• Study Start: January 1, 2022
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (20)