Triple Antihypertensive Medication After Intracerebral Hemorrhage for Blood Pressure Control (TRIACT)

TRIple Antihypertensive Medication After Intracerebral Hemorrhage for Blood Pressure ConTrol With the TRICH Score

Intracerebral hemorrhage (ICH) is the second most common form of stroke, with an incidence of around 3000 cases per year in Hong Kong. Although it only accounts for around 20-30% of all strokes, ICH is the most severe form of stroke, contributing to 50% of all stroke mortality and the greatest disability burden in stroke. For those who survive their ICH, they are at high risk of ICH recurrence, stroke, cardiovascular event and death. Hence, reducing these risks after ICH is a top priority to lessen the disease's healthcare and social burden.

Hypertension is the main driver for ICH, and achieving blood pressure (BP) control significantly reduces the risk of recurrent ICH, stroke and cardiovascular events. However, only 50% of ICH survivors achieved BP control after ICH. This is because ICH patients represent a unique hypertensive population with more difficult-to-control BPs, with many requiring ≥3 antihypertensive medications. Many reasons contribute to uncontrolled hypertension, but inadequate prescription of medication is the most actionable cause. The notion of an upfront prescription of a triple antihypertensive regimen (triple pill) soon after ICH could consequent better BP control, but there are concerns of excessive lowering of BP, particularly in older patients, which has been associated with increased mortality. This approach may also not be suitable for ICH patients with cerebral amyloid angiopathy where the elevated admission BP may be due to acute hypertensive response rather than underlying hypertension. Additionally, the general use of upfront triple pill in all ICH would have healthcare implications, as triple pills are more expensive compared to conventional antihypertensive medications.

To facilitate individualized treatment, a predictive score, the TRICH score, was recently developed and validated to identify patients who require triple pills after ICH. Therefore, the current TRIACT study aims to test the clinical application and benefit of the TRICH score for the upfront prescription of triple antihypertensive medication after ICH to enable prompt achievement of BP control.

Study Overview

• Status: Recruiting
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: Exforge HCT® or Three Individual drug amlodipine + valsartan + hydrochlorothiazide

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kay Cheong TEO; Phone Number: +852 2255 5318; Email: kcteo@hku.hk

Study Locations

• Hong Kong
  • Hong Kong
    • Hong Kong, Hong Kong, Hong Kong
      • Not yet recruiting
      • Princess Margaret Hospital
      • Contact: Jerome Hiu Fung WU; Phone Number: +852 6461 1080; Email: hf.wu@ha.org.hk
    • Hong Kong, Hong Kong, Hong Kong
      • Recruiting
      • Queen Mary Hospital
      • Contact: Kay Cheong TEO; Phone Number: +852 2255 5318; Email: kcteo@hku.hk
    • Hong Kong, Hong Kong, Hong Kong
      • Not yet recruiting
      • Ruttonjee Hospital
      • Contact: Chung Hon KWAN; Phone Number: +852 5928 3354; Email: kch076@ha.org.hk
    • Hong Kong, Hong Kong, Hong Kong
      • Not yet recruiting
      • Yan Chai Hospital
      • Contact: Joshua Wai Ming FOK; Phone Number: +852 6626 4603; Email: fwm471@ha.org.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Spontaneous ICH
2. Age ≥18 years
3. Premorbid modified Rankin Scale of ≤3
4. TRICH score ≥3
5. Within 1 week of ICH

Exclusion Criteria:

1. Glasgow coma score <9
2. Expected life expectancy of six months
3. Admission SBP <160mmHg
4. Severe renal impairment, estimated glomerular filtration rate using CKD-EPI formula <30 ml/min/1.73m2
5. Inability to perform home BP monitoring
6. Inability to participate in follow-up activity
7. Hypersensitivity to study drug
8. Known contraindication to amlodipine
9. Known contraindication to valsartan
10. Known contraindication to hydrochlorothiazide
11. Any conditions that investigator deems that patient is not suitable of any component of the triple pill or antihypertensive medications in general

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group
Active Comparator: Triple antihypertensive medication group; Triple antihypertensive medication Amlodipine 5mg/ Valsartan 160mg/ Hydrochlorothiazide 12.5mg, either as triple pill or three individual component drugs, on Day 3 after ICH. Dosage will be increased to Amlodipine 10/ Valsartan 160/ Hydrochlorothiazide 25, if SBP remained >130 mmHg on Day 7, or early if deemed necessary. Further anti-hypertensive medication titration will be made by the research team in consultation with the treating medical team as appropriate during the study period.	Drug: Exforge HCT® or Three Individual drug amlodipine + valsartan + hydrochlorothiazide; Three antihypertensive medication will be prescribed, either as a fixed-dose, single-pill combination (triple pill) containing three antihypertensive agents with complementary mechanisms of action: amlodipine 5mg, valsartan 160mg, and hydrochlorothiazide 12.5mg, or as three individual drugs. Use of the triple pill will depend on the patient's ability to swallow an intact tablet (it cannot be crushed) and on local availability. This specific combination targets multiple pathways involved in blood pressure regulation: calcium channel blockade reduces peripheral vascular resistance, angiotensin II receptor blockade inhibits the renin-angiotensin-aldosterone system, and thiazide diuresis reduces plasma volume and further lowers vascular resistance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypertension Control	Controlled hypertension (office SBP <130 mmHg) 1 month after ICH	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypertension Control Rate	Controlled hypertension rate at 3, 6 and 12 months after ICH	3, 6 and 12 months after ICH
Blood Pressure changes post ICH	Change of BP from admission to one and three months	At admission time, 1 and 3 months after ICH
Ambulatory Blood Pressure	24-hour ambulatory BP at one and three months after ICH	At one and three months after ICH
Drug Safety	Drug safety by types, frequency and severity of adverse events (AEs)	1 year
Drug tolerability	Drug tolerability by the rate of treatment withdrawal due to AEs	1 year
Treatment Satisfaction	Adherence to Refills and Medications Scale (ARMS-12) at 3 and 12 months; Patient satisfaction survey with the Treatment Satisfaction Questionnaire for Medication (TSQM) at 3 and 12 months	At 3 and 12 months after ICH
Cerebral and Cardiovascular Recurrence	Recurrent ICH, stroke, cardiovascular events at 12 months	1 year

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: Princess Margaret Hospital, Hong Kong; Ruttonjee Hospital, Hong Kong; Yan Chai Hospital

Publications and helpful links

General Publications

• Biffi A, Teo KC, Castello JP, Abramson JR, Leung IYH, Leung WCY, Wang Y, Kourkoulis C, Myserlis EP, Warren AD, Henry J, Chan KH, Cheung RTF, Ho SL, Anderson CD, Gurol ME, Viswanathan A, Greenberg SM, Lau KK, Rosand J. Impact of Uncontrolled Hypertension at 3 Months After Intracerebral Hemorrhage. J Am Heart Assoc. 2021 Jun;10(11):e020392. doi: 10.1161/JAHA.120.020392. Epub 2021 May 15.
• So CH, Yeung C, Ho RW, Hou QH, Sum CHF, Leung W, Wong YK, Liu KCR, Kwan HH, Fok J, Yip EK, Sheng B, Yap DY, Leung GKK, Chan KH, Lau GKK, Teo KC. Triple Antihypertensive Medication Prediction Score After Intracerebral Hemorrhage (the TRICH Score). Neurology. 2025 May 13;104(9):e213560. doi: 10.1212/WNL.0000000000213560. Epub 2025 Apr 4.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Blood pressure control; Intracerebral Hemorrhage; Triple antihypertensive medication
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Intracranial Hemorrhages; Pathological Conditions, Signs and Symptoms; Cerebral Hemorrhage; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Amino Acids; Amino Acids, Essential; Sulfonamides; Sulfones; Tetrazoles; Chlorothiazide; Benzothiadiazines; Thiazides; Valine; Amino Acids, Branched-Chain; Valsartan; Hydrochlorothiazide; Exforge HCT
• Other Study ID Numbers: TKC202505

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No