Clinical trial NCT05766865: Effect and Safety of Surgical Intervention for Severe Spontaneous Intracerebral Hemorrhage Patients on Long-term Oral Antiplatelet Treatment
Official title: Effect and Safety of Surgical Intervention for Severe Spontaneous Intracerebral Hemorrhage Patients on Long-term Oral Antiplatelet Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Severe Spontaneous Intracranial Hemorrhage
Long-term Antiplatelet Treatment
Emergency Surgery
Complications
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Chao Yang Hospital
name: Beijing Shuyi Hospital
name: Beijing Anzhen Hospital
name: Guangzhou Red Cross Hospital
name: Beijing Pinggu District Hospital
First posted: 2023-03-13
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All severe spontaneous intracerebral hemorrhage (SSICH) patients except those not on long-term oral antiplatelet treatment (LOAPT) receiving conservative treatment.

Brief summary: Background: Despite the capability of emergency surgery to reduce the mortality of severe spontaneous intracranial hemorrhage (SSICH) patients, the effect and safety of surgical treatment for severe spontaneous intracranial hemorrhage (SSICH) patients receiving long-term oral antiplatelet treatment (LOAPT) remains unclear. In consideration of this, the cohort study is aimed at figuring out the effect and safety of emergency surgery for SSICH patients on LOAPT.

Methods: As a multicenter and prospective cohort study, it will be conducted across 7 representative clinical centers. Starting in September 2019, the observation is scheduled to be completed by December 2022, with a total of 450 SSIC H patients recruited. The information on clinical, radiological, and laboratory practices will be recorded objectively. All of the patients will be monitored until death or 6 months after the occurrence of primary hemorrhage.

Results: In this study, two comparative cohorts and an observational cohort will be set up. The primary outcome is the effect of emergency surgery, which is subject to assessment using the total mortality and comparison in the survival rate of SSICH patients on LOAPT between surgical treatment and conservative treatment. The second outcome is the safety of surgery, with the postoperative hemorrhagic complication which is compared between the operated SSICH patients on and not on LOAPT. Based on the observation of the characteristics and outcome of SSICH patients on LOAPT, the ischemic events after discontinuing LOAPT will be further addressed, and the coagulation function assessment system for operated SSICH patients on LOAPT will be established.

Conclusions: In this study, we will investigate the effect and safety of emergency surgery for SSICH patients on LOAPT, which will provide an evidence for management in the future.


Eligibility criteria: Inclusion Criteria:

* (1) 18-75 years old;
* (2) non-traumatic intracerebral hemorrhage;
* (3) severe intracerebral hemorrhage, which was defined as patients with supratentorial bleeding volume \> 30 ml, infratentorial bleeding volume \> 10 ml, midline shift \> 1 cm, or large intraventricular hematoma;
* (4) Glasgow coma score (GCS) \< 13;
* (5) family members agree to provide an informed written consent.

Exclusion Criteria:

* (1) patients had cerebrovascular diseases, e.g., intracranial aneurysm or vascular malformation, and intracranial tumors, which were associated with hemorrhage;
* (2) hemorrhagic transformation of cerebral infarction;
* (3) hemorrhage caused by venous thrombosis;
* (4) patients with severe coagulation disorder, e.g., hemophilia;
* (5) patients with coagulation dysfunction caused by malignant tumor, hepatic insufficiency, renal dysfunction, thrombocytopenia, coagulation diseases, and so on;
* (6) patients receiving other anticoagulation medications (vitamin K antagonist and new oral anticoagulants);
* (7) patients not on LOAPT who receive conservative treatment;
* (8) the patients who died before or on arriving at the hospital and within a short period (6 h) after admission.

Primary outcomes:
measure: Total mortality
timeFrame: From admission to 6 months after the occurrence primary hemorrhage
Secondary outcomes:
measure: Postoperative intracranial bleeding
timeFrame: Within one week after surgery
Other outcomes:
Locations:
city: Beijing
country: China
facility: Capital Medical University Affiliated Beijing Tiantan Hospital
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Shuo Wang
role: STUDY_CHAIR
References:
citation: Cordonnier C, Demchuk A, Ziai W, Anderson CS. Intracerebral haemorrhage: current approaches to acute management. Lancet. 2018 Oct 6;392(10154):1257-1268. doi: 10.1016/S0140-6736(18)31878-6.
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.
citation: Morgenstern LB, Hemphill JC 3rd, Anderson C, Becker K, Broderick JP, Connolly ES Jr, Greenberg SM, Huang JN, MacDonald RL, Messe SR, Mitchell PH, Selim M, Tamargo RJ; American Heart Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010 Sep;41(9):2108-29. doi: 10.1161/STR.0b013e3181ec611b. Epub 2010 Jul 22.
citation: Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM; STICH II Investigators. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013 Aug 3;382(9890):397-408. doi: 10.1016/S0140-6736(13)60986-1. Epub 2013 May 29.
citation: Goyal N, Tsivgoulis G, Malhotra K, Katsanos AH, Pandhi A, Alsherbini KA, Chang JJ, Hoit D, Alexandrov AV, Elijovich L, Fiorella D, Nickele C, Arthur AS. Minimally invasive endoscopic hematoma evacuation vs best medical management for spontaneous basal-ganglia intracerebral hemorrhage. J Neurointerv Surg. 2019 Jun;11(6):579-583. doi: 10.1136/neurintsurg-2018-014447. Epub 2019 Jan 7.
citation: Wang WZ, Jiang B, Liu HM, Li D, Lu CZ, Zhao YD, Sander JW. Minimally invasive craniopuncture therapy vs. conservative treatment for spontaneous intracerebral hemorrhage: results from a randomized clinical trial in China. Int J Stroke. 2009 Feb;4(1):11-6. doi: 10.1111/j.1747-4949.2009.00239.x.
citation: Xia Z, Wu X, Li J, Liu Z, Chen F, Zhang L, Zhang H, Wan X, Cheng Q. Minimally Invasive Surgery is Superior to Conventional Craniotomy in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis. World Neurosurg. 2018 Jul;115:266-273. doi: 10.1016/j.wneu.2018.04.181. Epub 2018 May 3.
citation: Lovelock CE, Molyneux AJ, Rothwell PM; Oxford Vascular Study. Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study. Lancet Neurol. 2007 Jun;6(6):487-93. doi: 10.1016/S1474-4422(07)70107-2.
citation: Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013 May 30;368(22):2113-24. doi: 10.1056/NEJMra1206531. No abstract available.
citation: Krittalak K, Sawanyawisuth K, Tiamkao S. Safety of withholding anticoagulation in patients with mechanical prosthetic valves and intracranial haemorrhage. Intern Med J. 2011 Oct;41(10):750-4. doi: 10.1111/j.1445-5994.2011.02579.x.
citation: Cahill RA, McGreal GT, Crowe BH, Ryan DA, Manning BJ, Cahill MR, Redmond HP. Duration of increased bleeding tendency after cessation of aspirin therapy. J Am Coll Surg. 2005 Apr;200(4):564-73; quiz A59-61. doi: 10.1016/j.jamcollsurg.2004.11.002.
citation: Korinth MC. Low-dose aspirin before intracranial surgery--results of a survey among neurosurgeons in Germany. Acta Neurochir (Wien). 2006 Nov;148(11):1189-96; discussion 1196. doi: 10.1007/s00701-006-0868-4. Epub 2006 Sep 21.
citation: de Miguel-Diez J, Gomez Martinez A, Montero Martinez C. Perioperative and Periprocedural Management of Antithrombotic Therapy. Arch Bronconeumol (Engl Ed). 2019 May;55(5):229-230. doi: 10.1016/j.arbres.2018.07.019. Epub 2018 Sep 5. No abstract available. English, Spanish.
citation: Douketis JD, Berger PB, Dunn AS, Jaffer AK, Spyropoulos AC, Becker RC, Ansell J. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):299S-339S. doi: 10.1378/chest.08-0675.
citation: Douketis JD, Bakhsh E. Perioperative management of antithrombotic therapy. Pol Arch Med Wewn. 2008 Apr;118(4):201-8.
citation: Wijdicks EF, Schievink WI, Brown RD, Mullany CJ. The dilemma of discontinuation of anticoagulation therapy for patients with intracranial hemorrhage and mechanical heart valves. Neurosurgery. 1998 Apr;42(4):769-73. doi: 10.1097/00006123-199804000-00053.
citation: Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol. 2005 Apr;27(2):81-90. doi: 10.1111/j.1365-2257.2005.00681.x.
citation: Kashuk JL, Moore EE, Sabel A, Barnett C, Haenel J, Le T, Pezold M, Lawrence J, Biffl WL, Cothren CC, Johnson JL. Rapid thrombelastography (r-TEG) identifies hypercoagulability and predicts thromboembolic events in surgical patients. Surgery. 2009 Oct;146(4):764-72; discussion 772-4. doi: 10.1016/j.surg.2009.06.054.
citation: Naidech AM, Jovanovic B, Liebling S, Garg RK, Bassin SL, Bendok BR, Bernstein RA, Alberts MJ, Batjer HH. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke. 2009 Jul;40(7):2398-401. doi: 10.1161/STROKEAHA.109.550939. Epub 2009 May 14.
citation: Prasad K, Mendelow AD, Gregson B. Surgery for primary supratentorial intracerebral haemorrhage. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000200. doi: 10.1002/14651858.CD000200.pub2.
citation: Li Y, Yang R, Li Z, Yang Y, Tian B, Zhang X, Wang B, Lu D, Guo S, Man M, Yang Y, Luo T, Gao G, Li L. Surgical Evacuation of Spontaneous Supratentorial Lobar Intracerebral Hemorrhage: Comparison of Safety and Efficacy of Stereotactic Aspiration, Endoscopic Surgery, and Craniotomy. World Neurosurg. 2017 Sep;105:332-340. doi: 10.1016/j.wneu.2017.05.134. Epub 2017 May 31.
citation: Yao Z, Ma L, You C, He M. Decompressive Craniectomy for Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis. World Neurosurg. 2018 Feb;110:121-128. doi: 10.1016/j.wneu.2017.10.167. Epub 2017 Nov 10.
citation: Zheng J, Li H, Zhao HX, Guo R, Lin S, Dong W, Ma L, Fang Y, Tian M, Liu M, You C. Surgery for Patients With Spontaneous Deep Supratentorial Intracerebral Hemorrhage: A Retrospective Case-Control Study Using Propensity Score Matching. Medicine (Baltimore). 2016 Mar;95(11):e3024. doi: 10.1097/MD.0000000000003024.
citation: Stein M, Misselwitz B, Hamann GF, Kolodziej M, Reinges MH, Uhl E. In-hospital mortality after pre-treatment with antiplatelet agents or oral anticoagulants and hematoma evacuation of intracerebral hematomas. J Clin Neurosci. 2016 Apr;26:42-5. doi: 10.1016/j.jocn.2015.05.069. Epub 2015 Dec 11.
citation: Khoo KF, Lepas B. Summary of evidence-based guideline: Periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Jan 7;82(1):95. doi: 10.1212/01.NEUROLOGY.0000437348.92583.18. No abstract available.
citation: Holzmacher JL, Reynolds C, Patel M, Maluso P, Holland S, Gamsky N, Moore H, Acquista E, Carrick M, Amdur R, Hancock H, Metzler M, Dunn J, Sarani B. Platelet transfusion does not improve outcomes in patients with brain injury on antiplatelet therapy. Brain Inj. 2018;32(3):325-330. doi: 10.1080/02699052.2018.1425804. Epub 2018 Jan 17.
citation: Katz J, Feldman MA, Bass EB, Lubomski LH, Tielsch JM, Petty BG, Fleisher LA, Schein OD; Study of Medical Testing for Cataract Surgery Team. Risks and benefits of anticoagulant and antiplatelet medication use before cataract surgery. Ophthalmology. 2003 Sep;110(9):1784-8. doi: 10.1016/S0161-6420(03)00785-1.