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Trial registered on ANZCTR


Registration number
ACTRN12611001289909
Ethics application status
Approved
Date submitted
15/12/2011
Date registered
16/12/2011
Date last updated
21/03/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Noninvasive cardiac output monitoring to optimise therapy for patients with poorly controlled hypertension: a randomised controlled trial
Scientific title
Comparison of blood pressure lowering efficacy between treatment based on a haemodynamic protocol guided by transcutaneous Doppler ultrasound and standard treatment in patients with poorly controlled (Stage 2) hypertension
Secondary ID [1] 273611 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 285406 0
Condition category
Condition code
Cardiovascular 285586 285586 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Adjustment or initiation of antihypertensive medications according to haemodynamic indices (cardiac output, systemic vascular resistance) measured by a transcutaneous Doppler ultrasound monitor. The haemodynamics-guided protocol gives general and specific recommendations to emergency department physicians. General recommendations will advice on the choice of antihypertensive class among 5 classses of antihypertensives recommended by the US guidelines (JNC 7) the 7th report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure - namely, Angiotensin Converting Enzyme Inhibitors, Calcium Channel Blockers, Angiotensin Receptor Blockers, Beta Blockers or Thiazide diuretics. Specific recommendations Drugs of choice and dosages (provided there are no contraindications and that reduced dosage is considered for geriatric patients and patients with impaired renal function): 1. SVRI-high protocol Drug recommendations, considering compelling indications:
1.Calcium channel blockers, e.g. Amlodipine, stepwise increments from 2.5mg daily, 5mg daily, 7.5mg daily to 10mg daily.
2.ACE inhibitors, e.g. lisinopril, stepwise increments from 5mg daily, 10mg daily, 15mg daily to 20mg daily.
3.Angiotensin II receptor blockers or alpha blockers can also be considered.

2. CI-high protocol
Drug recommendations, considering compelling indications:
1.Beta blockers, e.g. atenolol, stepwise increment from 25mg, 50mg, to 100mg daily.
2.Thiazide-like diuretics, e.g. Natrilix (slow-release), 1.5mg daily.

The mode of administration for all the above drugs is via the oral route, and the overall duration of use is 24 weeks. Doppler ultrasound haemodynamic measurements: A rapid and noninvasive portable device will be used to measure the cardiac function in hypertensive patients. The device (Ultrasonic Cardiac Output Monitor or USCOM, USCOM Limited, Sydney, Australia) uses Doppler ultrasound to measure the velocity of blood flow through the aortic or pulmonary valve and thus estimate CO and SVR. The software derives the stroke volume (SV) using algorithms based on the patient’s weight and height to determine the area of the valve. It also measures the heart rate (HR) and therefore gives a calculated CO (CO = SV x HR). Blood pressure is entered manually, from which the device calculates the mean arterial pressure (MAP) and thus SVR (SVR = MAP/CO). The transducer of the machine is placed on the patient’s chest in either the left parasternal position to measure trans-pulmonary blood flow, or the suprasternal position to measure trans-aortic blood flow. The procedure will take 5 - 10 minutes to complete. It will be performed at recruitment and on each follow up visit. (Weeks 2, 6, 12, 18 and 24)
Intervention code [1] 283894 0
Treatment: Drugs
Comparator / control treatment
Standard treatment according to established guidelines for hypertension (not based on haemodynamic parameters)

Standard treatment involves treatment prescribed by the same group of participating emergency department physicians following the US guidelines for management of hypertension ( (JNC 7) the 7th report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure - using the recommended drug classes Angiotensin Converting Enzyme Inhibitors, Calcium Channel Blockers, Angiotensin Receptor Blockers, Beta Blockers or Thiazide diuretics, as indicated for each patient; but without the guidance or knowledge of the patients' haemodynamic measurements.
Control group
Active

Outcomes
Primary outcome [1] 286150 0
Mean reduction of systolic BP from baseline

Blood pressure measurements
Blood pressure and heart rate will be measured in the right arm with an appropriately sized cuff using a standard oscillometric device.
Timepoint [1] 286150 0
Weeks 6, 12, 18 and 24
Secondary outcome [1] 295248 0
Mean reduction of diastolic BP

Blood pressure and heart rate will be measured in the right arm with an appropriately sized cuff using a standard oscillometric device.
Timepoint [1] 295248 0
Weeks 6, 12, 18 and 24
Secondary outcome [2] 295264 0
Proportion of patients achieving target BP (<140/90 mmHg)

Blood pressure and heart rate will be measured in the right arm with an appropriately sized cuff using a standard oscillometric device.
Timepoint [2] 295264 0
Weeks 6, 12, 18 and 24
Secondary outcome [3] 295265 0
Proportion of patients achieving normalization of haemodynamic parameters.

Transcutaneous Doppler ultrasound haemodynamic measurements
The transducer of the machine is placed on the patient's chest in either the left parasternal position to measure trans-pulmonary blood flow, or the suprasternal position to measure trans-aortic blood flow.

The procedure will take 5 - 10 minutes to complete and is noninvasive.
Timepoint [3] 295265 0
Weeks 2, 6, 12, 18 and 24

Eligibility
Key inclusion criteria
Patients aged 18 or above who attend the Emegency Department with mean systolic blood pressure > or =160mmHg or diastolic blood pressure >or =100mmHg at two or more blood pressure measurements at least 20 minutes apart, and on two separate occasions (i.e. 2 different calendar days within a 2-week period).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. The patient is pregnant or lactating.

2.The patient is unable to lie supine for USCOM assessment (e.g. due to shortness of breath, severe back pain, oxygen therapy, deformities or pain).

3.The patient is confused, psychiatrically disturbed, or unable to answer questions or communicate.

4.The patient is likely to be admitted to hospital (except admission to the Emergency Medicine Ward).

5. Hypertensive emergencies (e.g. acute stroke, acute coronary syndromes, acute left ventricular failure, acute aortic dissection, hypertensive encephalopathy.)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
26/03/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
202
Accrual to date
Final
Recruitment outside Australia
Country [1] 4021 0
Hong Kong
State/province [1] 4021 0

Funding & Sponsors
Funding source category [1] 284386 0
University
Name [1] 284386 0
The Chinese University of Hong Kong
Country [1] 284386 0
Hong Kong
Primary sponsor type
University
Name
The Chinese University of Hong Kong
Address
A&E Medicine Academic Unit
Prince of Wales Hospital
The Chinese University of Hong Kong
30-32 Ngan Shing Street
Shatin
Hong Kong (post-code is not necessary in Hong Kong)
Country
Hong Kong
Secondary sponsor category [1] 283316 0
None
Name [1] 283316 0
Address [1] 283316 0
Country [1] 283316 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286342 0
Joint New Territories East Cluster - Chinese University of Hong Kong Clinical Research Ethics Committee
Ethics committee address [1] 286342 0
Ethics committee country [1] 286342 0
Hong Kong
Date submitted for ethics approval [1] 286342 0
Approval date [1] 286342 0
Ethics approval number [1] 286342 0

Summary
Brief summary
In patients with poorly controlled hypertension, choosing the most appropriate antihypertensive agent can be an important decision and often has impact on management outcomes. Treatment options for hypertension are wide-ranging and include thiazide diuretics, angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers, and calcium channel blockers (CCB). Although expert recommendations in authoritative guidelines have focused on comparative analyses of cardiovascular outcomes, efficacy in reducing blood pressure, adverse effects, and cost, there is one other important parameter that has not been emphasized, which is the altered balance of the patient’s haemodynamics.

Essential hypertension can be classified into distinct subtypes depending on the primary haemodynamic derangement, which can either be increased cardiac output (CO), as more commonly seen in the younger age-group with sympathetic nervous system overactivity; or elevated systemic vascular resistance (SVR), as seen in older patients. Blood pressure may be lowered more effectively if therapy is targeted at the primary pathophysiological derangement. Accordingly, ACEIs, ARBs, and CCBs would be the drugs of choice for patients with elevated systemic vascular resistance, while thiazide diuretics and beta blockers would be the drugs of choice for patients with increased cardiac output. In practice, however, an antihypertensive drug is usually initiated without prior knowledge of the underlying haemodynamic derangement of the patient.

We hypothesise that an antihypertensive strategy that identifies the primary underlying haemodynamic derangement, and treats accordingly, will control blood pressure more effectively. A transcutaneous Doppler ultrasound monitor may be used to measure blood flow across the aortic or pulmonary valves and therefore estimate CO, stroke volume and SVR. It is portable, simple-to-use and may be operated by physicians or nurses.

We have performed a pilot study using this device to investigate the haemodynamic derangements of Emergency Department (ED) patients with poorly controlled hypertension. Patients aged 18 years or above who attended the ED with systolic blood pressure >or=160 or diastolic blood pressure >or=100 in two or more blood pressure measurements taken at least 20 minutes apart, on two separate occasions, were included. We found that 80% of the 49 patients included had increased SVR as the primary haemodynamic derangement. Moreover, in 28% of cases the patients’ existing anti-hypertensive medication did not match the derangements in CO and SVR. For example, several patients had low CO yet had been prescribed a beta-blocker or diuretic; while several others had high SVR yet they were not given ACEI, ARB or CCB. Further, in 35% of cases our ED physicians, who were blinded to the haemodynamic measurement data, chose to prescribe anti-hypertensives that would appear to be inappropriate based on the haemodynamic findings.

At present the body of evidence is that well-controlled blood pressure, however that may be achieved, improves an individual’s chances of prolonged life. We are not aware of any evidence that prescription appropriate to the primary underlying pathophysiological derangement (either elevated SVR or CO) is more effective at lowering blood pressure than prescription that seems inappropriate. However, conceptually it seems more sensible than not to treat the primary pathophysiological abnormality, and evidence is required to confirm whether or not this is true in practice. Therefore, we hypothesize that a protocol targeted at addressing the primary haemodynamic derangement ascertained by non-invasive Doppler ultrasound will lower blood pressure more effectively than standard, non-targeted management.

The aim of our study is to investigate whether the use of a protocol targeted at addressing the primary haemodynamic derangement ascertained by non-invasive Doppler ultrasound will lower blood pressure more effectively than standard, non-targeted, management, in emergency department patients with poorly controlled hypertension.

The setting is the Emergency Department (ED) of the Prince of Wales Hospital in Hong Kong, a 1,360-bed acute and tertiary-care hospital, which is also the regional Trauma and Emergency Centre serving the East New Terrtories area. It has an annual attendance of more than 150,000 new cases, of which on average at least 17% patients present with elevated blood pressure (unpublished report from an internal audit performed in March 2011, for the period 5-11 March 2011).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33538 0
Address 33538 0
Country 33538 0
Phone 33538 0
Fax 33538 0
Email 33538 0
Contact person for public queries
Name 16785 0
Dr. Stewart Chan
Address 16785 0
Emergency Department
Prince of Wales Hospital
30-32 Ngan Shing Street
Shatin
Hong Kong (post-code is not neccesary in Hong Kong)
Country 16785 0
Hong Kong
Phone 16785 0
+852 2632 1033
Fax 16785 0
Email 16785 0
[email protected]
Contact person for scientific queries
Name 7713 0
Dr. Stewart Chan
Address 7713 0
Emergency Department
Prince of Wales Hospital
30-32 Ngan Shing Street
Shatin
Hong Kong (post-code is not neccesary in Hong Kong)
Country 7713 0
Hong Kong
Phone 7713 0
+852 2632 1033
Fax 7713 0
Email 7713 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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