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Trial registered on ANZCTR


Registration number
ACTRN12616001370493
Ethics application status
Approved
Date submitted
27/09/2016
Date registered
4/10/2016
Date last updated
16/10/2019
Date data sharing statement initially provided
16/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of continuing or withholding blood pressure reducing drugs on the blood pressure stability and quality of recovery following day surgery procedures
Scientific title
Preoperative Renin-Angiotensin system antagonists and blood pressure responses during ambulatory procedures
Secondary ID [1] 290216 0
None
Universal Trial Number (UTN)
U1111-1188-0410
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haemodynamic instability 300394 0
Condition category
Condition code
Anaesthesiology 300256 300256 0 0
Anaesthetics

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Group II: Patients who are on Angiotensin converting enzyme inhibitor (ACEI) or Angiotensin receptor blocker (ARB) (either as monotherapy or in combination with other antihypertensive agents) AND took a dose of ACEI/ARB within 10 hours prior to surgery. This group is presumed to be under the influence of ACEI/ARB at the time of anaesthesia.

Medical and treatment details including antihypertensive therapy, of the participants will be collected from patient records. Details of anaesthetic management, intraoperative haemodynamic changes and postoperative recovery details will be collected at the end of surgery. With a telephone followup, the quality of recovery will be ascertained 24 hours following surgery.
Intervention code [1] 295985 0
Not applicable
Comparator / control treatment
Group 1: Patients who are not on any antihypertensive agents, who are on anti hypertensive therapy other than ACEIs or ARBs and patients on ACEIs or ARBs who ceased taking these drugs atleast 10 hours prior to surgery. This group is presumed to be devoid of ACEI/ARB effect at the time of anaesthesia.
Control group
Active

Outcomes
Primary outcome [1] 299734 0
Significant hypotension (yes/no) .

Hypotension will be defined in the following ways.
1. Based on systolic blood pressure: Drop of more than 30% systolic compared to baseline for minimum 5 minutes duration (that is, if these features are present over 2 consecutive readings).
2. Based on the change in mean arterial pressure: Decrease in mean arterial blood pressure <55 mm Hg regardless of the duration


Timepoint [1] 299734 0
1) a) first 15 minutes of anaesthetic induction 1b) over the duration of surgery 1c) over the duration of stay in recovery room
Primary outcome [2] 299735 0
Change in mean perioperative systolic blood pressure from mean pre-operative (baseline) measures (as a continuous variable) assessed using non-invasive blood pressure monitor
Timepoint [2] 299735 0
over the duration of surgery
Primary outcome [3] 299736 0
Preoperative hypertension assessed using non invasive blood pressure monitor. Hypertension will be classified as follows.
1. Stage I hypertension/inadequate control of blood pressure: Blood pressure of systolic greater than or equal to 140 mm Hg and/or diastolic greater than or equal to 90 mm Hg
2. Stage II hypertension: Blood pressure of systolicgreater than or equal to 160 mm Hg and/or diastolic greater than or equal to 100 mm Hg
3. Stage III (severe) hypertension: Blood pressure greater than or equal to 180 mm Hg and/or diastolic greater than or equal to 110 Hg
4. Stage IV hypertension: Systolic greater than or equal to 210 mm Hg or diastolic greater than or equal to 120 mm Hg.
Timepoint [3] 299736 0
on admission blood pressure
Secondary outcome [1] 327970 0
Length of stay in recovery room defined as the time difference between arrival to discharge from recovery room. This is collected by review of medical records
Timepoint [1] 327970 0
Time of discharge
Secondary outcome [2] 327971 0
Composite of occurrence of unplanned readmission or any major surgical or medical complications, assessed through review of medical records
Timepoint [2] 327971 0
24 hours post surgery
Secondary outcome [3] 328061 0
Primary outcome: Variability of systolic blood pressure assessed using non invasive blood pressure monitor
Timepoint [3] 328061 0
Over the duration of surgery
Secondary outcome [4] 328062 0
quality of recovery assessed using a 15 item validated postoperative recovery questionnaire called QoR-15.
Timepoint [4] 328062 0
baseline: on admission and
postoperative: 24 hours following surgery

Eligibility
Key inclusion criteria
All patients undergoing day-case procedures under general anaesthesia at TPCH during the study period.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patient refusing to participate, communication difficulty due to language barrier, emergency surgery.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
Binary outcomes will be analysed using Pearson’s Chi square tests or Fisher’s exact tests as indicated. Univariable and multivariable logistic regression analysis will be used to test associations between exposures of interest (e.g. Antihypertensive group) and binary outcomes (e.g. significant hypotension). Models will be adjusted for measured confounders such as age, BMI and comorbidities.
The differences between mean changes in blood pressure will be assessing using mean-comparison tests (t-tests or ANOVA). Further analyses will include univariable and multivariable linear regression analyses as indicated to test associations between exposures of interest and continuous variables. Mixed effects regression modeling techniques may be employed to study the effects of drug group and time of withdrawal on changes in blood pressure over time under anesthesia. An alpha value of 0.05 will be used to assess statistical significance.
An estimated total of 530 patients would be required to detect a significant difference (alpha=0.05, power 80%) between patients that were taking ACEI/ARBs prior to surgery compared to patients that were not, assuming the proportion of patients experiencing moderate hypotension was 0.60 compared to 0.46 for those whose last dose of ACEI/ARB was <10 hours and greater than or equal to 10 hours respectively. . We propose to recruit a total of n= 650 including dropouts and loss to follow ups.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 6717 0
The Prince Charles Hospital - Chermside
Recruitment postcode(s) [1] 14363 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 294581 0
Hospital
Name [1] 294581 0
Department of Anaesthesia, The Prince Charles Hospital
Address [1] 294581 0
The Prince Charles Hospital, Rode Road, Chermside, QLD 4032
Country [1] 294581 0
Australia
Primary sponsor type
Individual
Name
Usha Gurunathan
Address
Department of Anaesthesia, The Prince Charles Hospital, Rode Road, Chermside, QLD 4032
Country
Australia
Secondary sponsor category [1] 293450 0
None
Name [1] 293450 0
Address [1] 293450 0
Country [1] 293450 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296021 0
The Prince Charles Hospital, Human Research and Ethics committee
Ethics committee address [1] 296021 0
The Prince Charles Hospital, Rode Road, Chermside, Queensland- 4032
Ethics committee country [1] 296021 0
Australia
Date submitted for ethics approval [1] 296021 0
21/08/2016
Approval date [1] 296021 0
13/09/2016
Ethics approval number [1] 296021 0
HREC/16/QPCH/280

Summary
Brief summary
Ambulatory surgical procedures are increasingly being performed worldwide; patient complexities such as obesity, advanced age along with other medical conditions will be frequently encountered. Major perioperative morbidites or mortalities are reported to occur once in every 1000-day surgical cases according to a recent large review on approximately 250,000 cases. One of the significant predictors for adverse outcomes was hypertension. Increasing number of patients on ACEI and ARBs are seen undergoing day surgery procedures. While we have strong recommendations about preoperative beta-blockers, the evidence on these antihypertensives that act on the renin- angiotensin pathway is insufficient and controversial There is insufficient evidence on whether ACEI and ARBs should be continued or ceased before ambulatory surgeries. As there have been limited data in terms of recommendations on ACEI/ARB agonist in ambulatory surgeries, more research seems necessary to provide evidence on the risks of continuation these drugs, in terms of both high and low blood pressure responses.
Primary aim: To investigate the association between i)Preoperative angiotensinogen converting enzyme inhibitor (ACEI) and ii)angiotensin II receptor blocker (ARB) therapy and perioperative blood pressure changes in patients undergoing ambulatory surgical procedures
Secondary aim: 1. To study the haemodynamic influence of continuation of other antihypertensive agents. 2. To examine the effect of hemodynamic fluctuations on the quality of recovery and complication rates
Following ethics committee approval, preoperative data from the consented patients that undergo day surgery procedures will be collected from patient records and face-to-face interview. Patients are allowed to follow their medication order as per the surgical/ anaesthetic teams’ instructions. No specific instruction on the antihypertensive treatment shall be given for this study. The preoperative data collected include but not limited to the antihypertensive therapy details and the time of last dose of medication. Management of the case will be left to the anaesthetic team involved. The details on the anaesthetic management, intraoperative hemodynamic changes and postoperative recovery details will be collected at the end of surgery.
Endpoints measured:
Primary: Significant hypotension b. Change in mean perioperative systolic blood pressure from mean pre-operative measures. c) Variability in systolic blood pressure d) Preoperative hypertensionSecondary outcomes: Length of stay in recovery room. Unplanned readmission or any major surgical or medical complications, quality of recovery within 24 hours of the day-surgery procedure, correlation between the primary outcome measures Vs type antihypertensive agents and the timing of discontinuation in patients on monotherapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69266 0
Dr Usha Gurunathan
Address 69266 0
The Prince Charles Hospital, Rode Road, Chermside, Queensland,- 4032
Country 69266 0
Australia
Phone 69266 0
+61 7 3139 4000
Fax 69266 0
Email 69266 0
usha.gurunathan@health.qld.gov.au
Contact person for public queries
Name 69267 0
Mr Adrian Roe
Address 69267 0
Department of Urology, The Prince Charles Hospital, Rode Road, Chermside, Queensland,- 4032
Country 69267 0
Australia
Phone 69267 0
+61 7 3139 4000
Fax 69267 0
Email 69267 0
adrian.roe@health.qld.gov.au
Contact person for scientific queries
Name 69268 0
Dr Usha Gurunathan
Address 69268 0
The Prince Charles Hospital, Rode Road, Chermside, Queensland,- 4032
Country 69268 0
Australia
Phone 69268 0
+61 7 3139 4000
Fax 69268 0
Email 69268 0
usha.gurunathan@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data is not meaningful as the data will be deidentified and only the haemodynamics readings will be considered for analysis
What supporting documents are/will be available?
No other documents available
Summary results
No Results