Triple Antihypertensive Medication After Intracerebral Hemorrhage for Blood Pressure Control

Official title

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

Overview

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.

Interventions

• 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

Primary outcome measures

• Hypertension Control [Time frame: 1 month]

Secondary outcome measures (7)

• Hypertension Control Rate [Time frame: 3, 6 and 12 months after ICH]
• Blood Pressure changes post ICH [Time frame: At admission time, 1 and 3 months after ICH]
• Ambulatory Blood Pressure [Time frame: At one and three months after ICH]
• Drug Safety [Time frame: 1 year]
• Drug tolerability [Time frame: 1 year]
• Treatment Satisfaction [Time frame: At 3 and 12 months after ICH]
• Cerebral and Cardiovascular Recurrence [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• Spontaneous ICH
• Age ≥18 years
• Premorbid modified Rankin Scale of ≤3
• TRICH score ≥3
• Within 1 week of ICH

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Hong Kong · 4 centers

• Princess Margaret Hospital — Hong Kong
• Queen Mary Hospital — Hong Kong
• Ruttonjee Hospital — Hong Kong
• Yan Chai Hospital — Hong Kong

Publications

• 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. PMID 40184593
• 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. PMID 33998241

Identifiers

NCT: NCT07458880 · TKC202505

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗