Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage

NCT00226096 | Completed DMC

• 1 other identifier: NDA1INTERACT
• Study Type: interventional
• Target: 404
• Locations: 3 countries
• Sites: 20

Brief Summary

The purpose of the study is to determine whether lowering high blood pressure levels after the start of a stroke caused by bleeding in the brain (intracerebral haemorrhage) will reduce the chances of a person dying or surviving with a long term disability. The study will be undertaken in two phases: a vanguard phase in 400 patients, to plan for a main phase in 2000 patients.

Conditions

CVA (Cerebrovascular Accident); Cerebral Hemorrhage; Intracranial Hemorrhages

Keywords

Clinical Trial; Blood Pressure; CVA (Cerebrovascular Accident)

Outcome Measures

Primary Outcomes (1)

• Combination death and dependency, according to a 3-6 scores on the modified Rankin Score.

  3 months

Secondary Outcomes (1)

• All cause and cause-specific early neurological deterioration during the first 72 hours; haematoma expansion & cerebral oedema at 24 & 72 hours; ; functional disability; cognitive function; quality of life; mortality at 1 and 3 months

  24 and 72 hours, 1 and 3 months

Interventions

Labetalol Hydrochloride DRUG

Metoprolol tartrate DRUG

Hydralazine Hydrochloride DRUG

Glycerol Trinitrate DRUG

Phentolamine mesylate DRUG

Nicardipine DRUG

Urapidil DRUG

Esmolol DRUG

Clonidine DRUG

Enalaprilat DRUG

Nitroprusside DRUG

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 or above
• Acute stroke due to spontaneous ICH confirmed by clinical history \& CT scan
• At least 2 systolic BP measurements of \>/=150mmHg and \</=220mmHg, recorded 2 or more minutes apart
• Able to commence randomly assigned BP lowering regimen within 6 hours of stroke onset
• Able to be actively treated and admitted to a monitored facility e.g. HDU/ICU/acute stroke unit

You may not qualify if:

• Known definite contraindication to an intensive BP lowering regimen
• Known definite indication for intensive BP lowering regimen as (or more) intensive than the active treatment arm
• Definite evidence that the ICH is secondary to a structural abnormality in the brain
• Previous ischaemic stroke within 30 days
• A very high likelihood that the patient will die within the next 24 hours on the basis of clinical and/or radiological criteria
• Known advanced dementia or significant pre-stroke disability
• Concomitant medical illness that would interfere with outcome assessments and follow up
• Already booked for surgical evacuation of haematoma
• Previous participation in this trial or current participation in another investigational drug trial
• A high likelihood that the patient will not adhere to the study treatment and follow up regimen

Sponsors & Collaborators

• The George Institute: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (20)

Concord Hospital

Concord, New South Wales, 2138, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

John Hunter Hospital

Newcastle, New South Wales, 2310, Australia

Location

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

St Vincent's Hospital

Melbourne, Victoria, 3065, Australia

Location

Box Hill Hospital

Melbourne, Victoria, 3128, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

Austin Health

Melbourne, Victoria, Australia

Location

Monash Medical Centre

Melbourne, Victoria, Australia

Location

Sir Charles Gairdner Hospital

Perth, Western Australia, 6009, Australia

Location

Regional Coordinating Centre: Peking University First Hospital

Beijing, 100034, China

Location

Hospitals in China, c/o The George Institute China

Beijing, China

Location

Regional Coordinating Centre: Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Second Medical University

Shanghai, 200025, China

Location

North Shore Hospital

Auckland, New Zealand

Location

Christchurch Hospital

Christchurch, New Zealand

Location

Related Publications (20)

• Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B, Heeley E, Skulina C, Parsons MW, Kim JS, Tao QL, Li YC, Jiang JD, Tai LW, Zhang JL, Xu E, Cheng Y, Heritier S, Morgenstern LB, Chalmers J; INTERACT Investigators. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008 May;7(5):391-9. doi: 10.1016/S1474-4422(08)70069-3. Epub 2008 Apr 7.

  PMID: 18396107 RESULT

• 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

• Maegele M. Towards optimization in the use of hemostatic agents and blood products in the early treatment of patients with traumatic brain injury (TBI). Curr Opin Anaesthesiol. 2025 Apr 1;38(2):129-135. doi: 10.1097/ACO.0000000000001465. Epub 2025 Feb 14.

  PMID: 39945652 DERIVED

• You S, Zheng D, Yoshimura S, Ouyang M, Han Q, Wang X, Cao Y, Delcourt C, Song L, Arima H, Chen X, Liu CF, Lindley RI, Robinson T, Anderson CS, Chalmers J; INTERACT Investigators. Optimum Baseline Clinical Severity Scale Cut Points for Prognosticating Intracerebral Hemorrhage: INTERACT Studies. Stroke. 2024 Jan;55(1):139-145. doi: 10.1161/STROKEAHA.123.044538. Epub 2023 Nov 29.

  PMID: 38018833 DERIVED

• Sandset EC, Wang X, Carcel C, Sato S, Delcourt C, Arima H, Stapf C, Robinson T, Lavados P, Chalmers J, Woodward M, Anderson CS. Sex differences in treatment, radiological features and outcome after intracerebral haemorrhage: Pooled analysis of Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2. Eur Stroke J. 2020 Dec;5(4):345-350. doi: 10.1177/2396987320957513. Epub 2020 Sep 20.

  PMID: 33598552 DERIVED

• Wang X, Moullaali TJ, Li Q, Berge E, Robinson TG, Lindley R, Zheng D, Delcourt C, Arima H, Song L, Chen X, Yang J, Chalmers J, Anderson CS, Sandset EC. Utility-Weighted Modified Rankin Scale Scores for the Assessment of Stroke Outcome: Pooled Analysis of 20 000+ Patients. Stroke. 2020 Aug;51(8):2411-2417. doi: 10.1161/STROKEAHA.119.028523. Epub 2020 Jul 9.

  PMID: 32640944 DERIVED

• Wang X, Sandset EC, Moullaali TJ, Chen G, Song L, Carcel C, Delcourt C, Woodward M, Robinson T, Chalmers J, Arima H, Anderson CS; INTERACT2 Investigators. Determinants of the high admission blood pressure in mild-to-moderate acute intracerebral hemorrhage. J Hypertens. 2019 Jul;37(7):1463-1466. doi: 10.1097/HJH.0000000000002056.

  PMID: 31085948 DERIVED

• Chen R, Wang X, Anderson CS, Robinson T, Lavados PM, Lindley RI, Chalmers J, Delcourt C. Infratentorial Intracerebral Hemorrhage. Stroke. 2019 May;50(5):1257-1259. doi: 10.1161/STROKEAHA.118.023766.

  PMID: 30890109 DERIVED

• Delcourt C, Zheng D, Chen X, Hackett M, Arima H, Hata J, Heeley E, Al-Shahi Salman R, Woodward M, Huang Y, Robinson T, Lavados PM, Lindley RI, Stapf C, Davies L, Chalmers J, Anderson CS, Sato S; INTERACT Investigators. Associations with health-related quality of life after intracerebral haemorrhage: pooled analysis of INTERACT studies. J Neurol Neurosurg Psychiatry. 2017 Jan;88(1):70-75. doi: 10.1136/jnnp-2016-314414. Epub 2016 Oct 21.

  PMID: 27919055 DERIVED

• Song L, Sandset EC, Arima H, Heeley E, Delcourt C, Chen G, Yang J, Wu G, Wang X, Lavados PM, Huang Y, Stapf C, Wang J, Robinson TG, Chalmers J, Lindley RI, Anderson CS; INTERACT2 Investigators. Early blood pressure lowering in patients with intracerebral haemorrhage and prior use of antithrombotic agents: pooled analysis of the INTERACT studies. J Neurol Neurosurg Psychiatry. 2016 Dec;87(12):1330-1335. doi: 10.1136/jnnp-2016-313246. Epub 2016 May 13.

  PMID: 27178897 DERIVED

• Qiu M, Sato S, Zheng D, Wang X, Carcel C, Hirakawa Y, Sandset EC, Delcourt C, Arima H, Wang J, Chalmers J, Anderson CS; INTERACT Investigators*. Admission Heart Rate Predicts Poor Outcomes in Acute Intracerebral Hemorrhage: The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies. Stroke. 2016 Jun;47(6):1479-85. doi: 10.1161/STROKEAHA.115.012382. Epub 2016 May 10.

  PMID: 27165954 DERIVED

• Moullaali TJ, Sato S, Wang X, Rabinstein AA, Arima H, Carcel C, Chen G, Robinson T, Heeley E, Chan E, Delcourt C, Stapf C, Cordonnier C, Lindley RI, Chalmers J, Anderson CS; INTERACT Investigators. Prognostic significance of delayed intraventricular haemorrhage in the INTERACT studies. J Neurol Neurosurg Psychiatry. 2017 Jan;88(1):19-24. doi: 10.1136/jnnp-2015-311562. Epub 2016 Jan 8.

  PMID: 26746184 DERIVED

• Wang X, Arima H, Al-Shahi Salman R, Woodward M, Heeley E, Stapf C, Lavados PM, Robinson T, Huang Y, Wang J, Delcourt C, Anderson CS. Rapid Blood Pressure Lowering According to Recovery at Different Time Intervals after Acute Intracerebral Hemorrhage: Pooled Analysis of the INTERACT Studies. Cerebrovasc Dis. 2015;39(3-4):242-8. doi: 10.1159/000381107. Epub 2015 Mar 25.

  PMID: 25823544 DERIVED

• Yang J, Arima H, Wu G, Heeley E, Delcourt C, Zhou J, Chen G, Wang X, Zhang S, Yu S, Chalmers J, Anderson CS; INTERACT Investigators. Prognostic significance of perihematomal edema in acute intracerebral hemorrhage: pooled analysis from the intensive blood pressure reduction in acute cerebral hemorrhage trial studies. Stroke. 2015 Apr;46(4):1009-13. doi: 10.1161/STROKEAHA.114.007154. Epub 2015 Feb 24.

  PMID: 25712944 DERIVED

• Priglinger M, Arima H, Anderson C, Krause M; INTERACT Investigators. No relationship of lipid-lowering agents to hematoma growth: pooled analysis of the intensive blood pressure reduction in acute cerebral hemorrhage trials studies. Stroke. 2015 Mar;46(3):857-9. doi: 10.1161/STROKEAHA.114.007664. Epub 2015 Feb 5.

  PMID: 25657175 DERIVED

• Sato S, Heeley E, Arima H, Delcourt C, Hirakawa Y, Pamidimukkala V, Li Z, Tao Q, Xu Y, Hennerici MG, Robinson T, Tzourio C, Lindley RI, Chalmers J, Anderson CS; INTERACT Investigators; Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B, Heeley E, Skulina C, Parsons MW, Kim JS, Tao QL, Li YC, Jiang JD, Tai LW, Zhang LJ, Xu E, Cheng Y, Heritier S, Morgenstern LB, Chalmers J. Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1 and 2. J Neurol Neurosurg Psychiatry. 2015 Dec;86(12):1319-23. doi: 10.1136/jnnp-2014-309870. Epub 2015 Jan 14.

  PMID: 25589782 DERIVED

• Wang X, Arima H, Al-Shahi Salman R, Woodward M, Heeley E, Stapf C, Lavados PM, Robinson T, Huang Y, Wang J, Delcourt C, Anderson CS; INTERACT Investigators. Clinical prediction algorithm (BRAIN) to determine risk of hematoma growth in acute intracerebral hemorrhage. Stroke. 2015 Feb;46(2):376-81. doi: 10.1161/STROKEAHA.114.006910. Epub 2014 Dec 11.

  PMID: 25503550 DERIVED

• Delcourt C, Huang Y, Arima H, Chalmers J, Davis SM, Heeley EL, Wang J, Parsons MW, Liu G, Anderson CS; INTERACT1 Investigators. Hematoma growth and outcomes in intracerebral hemorrhage: the INTERACT1 study. Neurology. 2012 Jul 24;79(4):314-9. doi: 10.1212/WNL.0b013e318260cbba. Epub 2012 Jun 27.

  PMID: 22744655 DERIVED

• Arima H, Huang Y, Wang JG, Heeley E, Delcourt C, Parsons M, Li Q, Neal B, Chalmers J, Anderson C; INTERACT1 Investigators. Earlier blood pressure-lowering and greater attenuation of hematoma growth in acute intracerebral hemorrhage: INTERACT pilot phase. Stroke. 2012 Aug;43(8):2236-8. doi: 10.1161/STROKEAHA.112.651422. Epub 2012 Jun 7.

  PMID: 22678090 DERIVED

• Arima H, Anderson CS, Wang JG, Huang Y, Heeley E, Neal B, Woodward M, Skulina C, Parsons MW, Peng B, Tao QL, Li YC, Jiang JD, Tai LW, Zhang JL, Xu E, Cheng Y, Morgenstern LB, Chalmers J; Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial Investigators. Lower treatment blood pressure is associated with greatest reduction in hematoma growth after acute intracerebral hemorrhage. Hypertension. 2010 Nov;56(5):852-8. doi: 10.1161/HYPERTENSIONAHA.110.154328. Epub 2010 Sep 7.

  PMID: 20823381 DERIVED

MeSH Terms

Conditions

Stroke; Cerebral Hemorrhage; Intracranial Hemorrhages

Interventions

Labetalol; Metoprolol; Hydralazine; Nitroglycerin; Phentolamine; Nicardipine; urapidil; esmolol; Clonidine; Enalaprilat; Nitroprusside

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Salicylamides; Amides; Amines; Phenoxypropanolamines; Propanolamines; Propanols; Phthalazines; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitro Compounds; Imidazoles; Azoles; Dihydropyridines; Pyridines; Imidazolines; Enalapril; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds

Study Officials

• Craig Anderson, PhD

  The George Institute

  PRINCIPAL INVESTIGATOR

• Bruce Neal, PhD

  The George Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 23, 2005
• First Posted: September 26, 2005
• Study Start: November 1, 2005
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: June 26, 2008

Record last verified: 2008-06

Locations

NZ (2); CN (3); AU (15)