The Third, Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial

NCT03209258 | Completed DMC

• 1 other identifier: ICH-WCH&GI
• Study Type: interventional
• Target: 7,067
• Locations: 1 country
• Sites: 1

Brief Summary

Continued uncertainty exists over benefits of early intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH), related to the non-significant primary outcomes, patient selection, and discordant results of INTERACT2 and ATACH-II. We designed INTERACT3 to determine the effectiveness of a goal-directed care bundle of active management (intensive BP lowering, glycemic control, treatment of pyrexia and reversal of anticoagulation) vs. usual care in ICH. INTERACT3 is a large-scale pragmatic clinical trial to provide reliable evidence over the effectiveness of a widely applicable goal-directed care bundle in acute ICH.

Conditions

Cerebral Hemorrhage; Stroke; Hypertension; Diabetes; Anticoagulant-induced Bleeding; Cerebral Vascular Disorder; Brain Disorder; Hemorrhage; Intracranial Hemorrhages; Cardiovascular Diseases; Central Nervous System Diseases

Keywords

Stroke; Intracerebral Hemorrhage; Care Bundle; Clinical Trial; Stepped-wedge Cluster; Management; Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Shift ('improvement') in functional recovery (death or disability) defined by the modified Rankin Scale (mRS)

  modified Rankin Scale is a measure of physical function at 6 months, analyzed as an ordinal outcome (categories scored as 0 'no symptoms' to 5 as 'fully dependent, and 6 as death)

  6 months

Secondary Outcomes (7)

• Shift ('improvement') in survival and neurological impairment defined by scores on the National Institutes of Health Stroke Scale (NIHSS)

  7 days

• Death or disability defined by scores of 3-6 on the mRS

  6 months

• Death

  6 months

• Disability defined by scores 3-5 on the mRS

  6 months

• Health-related quality of life (HRQoL)

  6 months

Study Arms (2)

Goal-directed care bundle

OTHER

Management policy to receive a goal-directed care bundle that involves the rapid correction (\<1 hour) of physiological variables as soon as the abnormality is recognised and for the control to be maintained in patients for 7 days or hospital discharge (or death, if sooner)

Other: Care bundle of active management

Usual care group

OTHER

Patients receive the usual management based on local guidelines and hospital's individual policy.

Other: Usual care

Interventions

Care bundle of active management OTHER

1. Intensive BP lowering to systolic target of \<140mmHg; 2. Glucose control target 6.1-7.8 mmol/l for non-diabetic; 7.8-10.0 mmol/l for diabetic patients; 3. Treatment of pyrexia to a target body temperature ≤37.5 ℃; 4. Reversal of anticoagulation to target INR \<1.5 involving use of vitamin K and prothrombin complex concentrate (PCC) or alternatively, fresh frozen plasma (FFP). As the trial is an assessment of care bundle of physiological management, there is some flexibility in the use of particular BP lowering agents and antipyretic agents to achieve targets.

Also known as: Early intensive BP lowing, Intensive glucose control, Early treatment of pyrexia, Reversal of anticoagulation

Goal-directed care bundle

Usual care OTHER

Usual care decisions about the location of care delivery, investigations, monitoring, and all treatments will be made by the treating clinical team.

Usual care group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years
• Acute stroke syndrome that is due to presumed spontaneous ICH, confirmed by clinical history and a CT scan within 6 hours of stroke onset without/without contrast, and if an CT angiogram is also undertaken as part of routine care.
• Presentation to hospital within 6 hours of stroke onset.

You may not qualify if:

• Definite evidence that the ICH is secondary to a structural abnormality in the brain (eg an AVM, intracranial aneurysm, tumour, trauma, or previous cerebral infarction) or previous thrombolysis.
• A high likelihood that the patient will not adhere to the study treatment and follow-up regimen. In each case, the decision about the patient's eligibility will be based on the attending clinician's interpretation of the above eligibility criteria.

Sponsors & Collaborators

• The George Institute for Global Health, China: lead
• West China Hospital: collaborator
• Sichuan Credit Pharmaceutical Co., Ltd.: collaborator
• Takeda: collaborator
• National Institute for Health Research, United Kingdom: collaborator
• Department for International Development, United Kingdom: collaborator
• UK Research and Innovation: collaborator
• Medical Research Council: collaborator

Study Sites (1)

West China Hospital

Chengdu, Sichuan, China

Location

Related Publications (9)

• Ren X, Li Q, Ouyang M, Billot L, Chen X, Venturelli PM, de Silva A, Nguyen TH, Wahab KW, Pandian JD, Wasay M, Pontes-Neto OM, Abanto C, Arauz A, You C, Ma L, Hu X, Anderson C, Wang X, Song L; as the INTERACT3 Investigators. Mediation Analysis to Identify Individual Component Effects of the Care Bundle to Improve Functional Outcome After ICH in the INTERACT3 Study. Neurology. 2025 Oct;105(7):e214070. doi: 10.1212/WNL.0000000000214070. Epub 2025 Sep 12.

  PMID: 40939125 DERIVED

• Hu X, Ouyang M, Xu J, Liu Y, Li X, Jiang Y, Chen X, Billot L, Li MBiostat Q, Malavera A, Venturelli PMO, de Silva A, Thang NH, Wahab KW, Pandian JD, Wasay M, Pontes-Neto OM, Abanto C, Arauz A, Li Z, Chen M, Wang X, Yang C, Xin X, Jiang D, Zheng J, Yu Z, Xiao A, Tao C, Chen L, Wu B, Li H, Anderson CS, You C, Song L, Ma L; INTERACT3 Investigators. Surgical outcomes from haematoma evacuation for intracerebral haemorrhage in the INTERACT3 study. Lancet Reg Health West Pac. 2025 Aug 28;62:101669. doi: 10.1016/j.lanwpc.2025.101669. eCollection 2025 Sep.

  PMID: 40927652 DERIVED

• Wang X, Ren X, Li Q, Ouyang M, Chen C, Delcourt C, Chen X, Wang J, Robinson T, Arima H, Ma L, Hu X, You C, Li G, Jie Y, Lin Y, Billot L, Munoz-Venturelli P, Martins S, Pontes-Neto OM, Liu L, Chalmers J, Carcel C, Song L, Anderson CS; INTERACT Investigators. Effects of blood pressure lowering in relation to time in acute intracerebral haemorrhage: a pooled analysis of the four INTERACT trials. Lancet Neurol. 2025 Jul;24(7):571-579. doi: 10.1016/S1474-4422(25)00160-7.

  PMID: 40541207 DERIVED

• Ouyang M, Anjum A, Mc Cawley FG, Wasay M, Ma L, Hu X, Chen X, Malavera A, Li X, Venturelli PM, Silva HA, Thang NH, Wahab KW, Pandian JD, Pontes-Neto OM, Abanto C, Cano-Nigenda V, Arauz A, You C, Jan S, Song L, Anderson CS, Liu H; INTERACT3 Investigators. Implementation of a goal-directed Care Bundle for intracerebral hemorrhage: Results of embedded process evaluation in the INTERACT3 trial. PLOS Glob Public Health. 2024 Dec 19;4(12):e0003711. doi: 10.1371/journal.pgph.0003711. eCollection 2024.

  PMID: 39700102 DERIVED

• Ma L, Hu X, Song L, Chen X, Ouyang M, Billot L, Li Q, Malavera A, Li X, Munoz-Venturelli P, de Silva A, Thang NH, Wahab KW, Pandian JD, Wasay M, Pontes-Neto OM, Abanto C, Arauz A, Shi H, Tang G, Zhu S, She X, Liu L, Sakamoto Y, You S, Han Q, Crutzen B, Cheung E, Li Y, Wang X, Chen C, Liu F, Zhao Y, Li H, Liu Y, Jiang Y, Chen L, Wu B, Liu M, Xu J, You C, Anderson CS; INTERACT3 Investigators. The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial. Lancet. 2023 Jul 1;402(10395):27-40. doi: 10.1016/S0140-6736(23)00806-1. Epub 2023 May 25.

  PMID: 37245517 DERIVED

• Billot L, Song L, Hu X, Ma L, Ouyang M, Chen X, You C, Anderson CS; INTERACT3 Investigators. Statistical Analysis Plan for the INTEnsive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial: A Stepped-Wedge Cluster Randomized Controlled Trial. Cerebrovasc Dis. 2023;52(3):251-254. doi: 10.1159/000526384. Epub 2022 Sep 5.

  PMID: 36063792 DERIVED

• Ouyang M, Anderson CS, Song L, Malavera A, Jan S, Cheng G, Chu H, Hu X, Ma L, Chen X, You C, Liu H. Process Evaluation of an Implementation Trial: Design, Rationale, and Early Lessons Learnt From an International Cluster Clinical Trial in Intracerebral Hemorrhage. Front Med (Lausanne). 2022 Jun 15;9:813749. doi: 10.3389/fmed.2022.813749. eCollection 2022.

  PMID: 35783649 DERIVED

• Song L, Hu X, Ma L, Chen X, Ouyang M, Billot L, Li Q, Munoz-Venturelli P, Abanto C, Pontes-Neto OM, Antonio A, Wasay M, Silva A, Thang NH, Pandian JD, Wahab KW, You C, Anderson CS; INTERACT3 investigators. INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial. Trials. 2021 Dec 20;22(1):943. doi: 10.1186/s13063-021-05881-7.

  PMID: 34930428 DERIVED

• Ouyang M, Anderson CS, Song L, Jan S, Sun L, Cheng G, Chu H, Hu X, Ma L, Chen X, You C, Liu H. Implementing a Goal-Directed Care Bundle after Acute Intracerebral Haemorrhage: Process Evaluation for the Third INTEnsive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial Study in China. Cerebrovasc Dis. 2022;51(3):373-383. doi: 10.1159/000520669. Epub 2021 Dec 20.

  PMID: 34929690 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Stroke; Hypertension; Diabetes Mellitus; Cerebrovascular Disorders; Brain Diseases; Hemorrhage; Intracranial Hemorrhages; Cardiovascular Diseases; Central Nervous System Diseases

Interventions

Anticoagulation Reversal

Condition Hierarchy (Ancestors)

Nervous System Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Hemostatic Techniques; Therapeutics

Study Officials

• Craig S Anderson, PhD

  The George Institute for Global Health, China

  PRINCIPAL INVESTIGATOR

• Chao You, PhD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Director

Model Details: Stepped-wedge Cluster Randomised Trial

Study Record Dates

• First Submitted: July 1, 2017
• First Posted: July 6, 2017
• Study Start: December 12, 2017
• Primary Completion: October 12, 2022
• Study Completion: November 17, 2022
• Last Updated: November 29, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)