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Trial registered on ANZCTR


Registration number
ACTRN12616000303448
Ethics application status
Approved
Date submitted
2/03/2016
Date registered
8/03/2016
Date last updated
28/01/2020
Date data sharing statement initially provided
28/01/2020
Date results information initially provided
28/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The prevalence and impact of postprandial hypotension in elderly survivors of critical illness.
Scientific title
An exploratory study to estimate the prevalence, mechanisms underlying and impact of postprandial hypotension in survivors of critical illness aged 65 years and greater.
Secondary ID [1] 288673 0
None
Universal Trial Number (UTN)
U1111-1180-3305
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical illness 297870 0
Postprandial hypotension 297871 0
Condition category
Condition code
Oral and Gastrointestinal 298044 298044 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cardiovascular 298056 298056 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Seventy five consecutive patients aged 65 years old or older who receive at least 48 hours of care in ICU will be evaluated at 3 months (+/- 1 month) following discharge from ICU.

We will document basic demographic data, all current medications (prior to hospital admission and on discharge from ICU, with particularly reference to the presence of anti-hypertensive drugs which will be analysed as pre-defined sub-group) and concurrent chronic illnesses and use validated questionnaires to evaluate falls/symptoms of PPH, frailty (a syndrome characterised by the loss of physiologic and cognitive reserves that will be quantified via the Canadian Study on Health and Ageing Clinical Frailty Scale, a well-validated 9-point assessment tool designed to quantify frailty), independent activity of daily living (iADLs) and quality of life using questionnaires. The later will be quantified using the generic quality of life instrument (EQ-5D-5L), which provide a utility score and visual analogue scale score.

On the study day, patients will present to the Department of Nuclear Medicine, PET and Bone Densitometry or Diabetes Centre (where we have a gamma camera used exclusively for research purposes) at the Royal Adelaide Hospital following an overnight fast (12 hrs solids and liquids). Smoking will be prohibited for 12 hours prior to and on the study day. Participants will be instructed to consume their usual medications on the morning of the study with a small sip of water. Instructions regarding glucose-lowering drugs will be provided to patients with diabetes by a consultant endocrinologist (Dr Phillips). Following informed consent participants will be asked to rest quietly in a chair for 10 minutes. Lying, seated, and standing blood pressures will then be measured. Following these measurements, an intravenous cannula will be inserted into an antecubital vein for blood sampling. Subjects will then be seated with their back against a gamma camera with an automated blood pressure cuff placed around the opposite arm for measurement of blood pressure and heart rate. Participants will sit quietly for a further 5 minutes and following baseline measurements participants will consume a 300mL drink (Glucaid) containing 75g glucose labelled with 0.1g of Octanoic acid and 20MBq 99mTc-calcium phytate. Scintigraphy and a breath test will be used to assess gastric emptying for 4 hours. The breath test will require the participant to breathe into a collection tube at 5 minute intervals for the first hour and then every 15 minutes thereafter. Scintigraphic gastric emptying curves (expressed as % of the maximum content of the total stomach) will be derived and the content of the total stomach at t = 0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 minutes calculated. The duration of the lag phase and the 50% emptying time (T50) will also be obtained.

Blood pressure (systolic and diastolic) and heart rate will be assessed prior to ingestion of the drink and at 3 min intervals until completion of the study i.e. t=240mins. After the study, the subject’s blood pressure will be monitored at 15 min intervals for a minimum of 1 hour to ensure the subject's blood pressure has returned to baseline levels for safety reasons. Blood samples will be obtained immediately prior to ingestion of the drink (t = -3 minutes) then every 15 minutes until t = 240 minutes for blood glucose. We will also measure serum insulin, gastrointestinal hormones (GLP-1 and GIP) and catecholamines (RAH Protocol 131217) at baseline and every 15 minutes until t=60, every 30 minutes until t=120 and then hourly until t=240. Sensations of appetite and dizziness will be evaluated using a visual analogue scale immediately prior to ingestion of the drink (t = -3 minutes) then every 15 minutes until t = 240 minutes.

Upon completion of the gastric emptying study, the intravenous cannula will then be removed. Then Autonomic nerve function will be assessed using standardised cardiovascular reflex tests using ANSAR Autonomic Nervous System monitoring technology. Parasympathetic function will be calculated by the variation (R - R interval) of the HR during deep breathing and the immediate heart rate response to standing ("30:15" ratio). Sympathetic function will be assessed by the fall in systolic blood pressure in response to standing.

To evaluate the trajectory of PPH symptoms, severity and impact over time, participants will be approached at 12 months and three years to complete an identical set of measurements. Prior to approaching patients we will determine whether hospital electronic repositories (OACIS) indicate that the patient has died. Once this is excluded we will contact the participant. The 12 month and three year visits will be identical to those conducted at three months. In addition we will quantify re-hospitalisation during this period.
Intervention code [1] 294092 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 297562 0
The prevalence of postprandial hypotension in survivors of critical illness who are aged 65 years and older. (by monitoring blood pressure and heart rate response to ingestion of a 300mL glucaid drink using an automated blood pressure cuff)
Timepoint [1] 297562 0
BP and HR will be assessed 5 minutes before the ingestion of the drink and at 3 min intervals until 240 minutes. This will occur at all three study visits (at 3, 12 and 36 months post discharge from hospital)
Secondary outcome [1] 321405 0
Autonomic dysfunction in elderly survivors of critical illness (using standardised cardiovascular reflex tests using Autonomic Nervous System Monitoring Technology, and calculating the variation of R-R interval of HR during deep breathing, and determining the heart rate and blood pressure response to standing.)
Timepoint [1] 321405 0
Autonomic function will be assessed after the completion of the gastric emptying study i.e. 240 minutes. This will occur at all three study visits (at 3, 12, 36 months post discharge from hospital).
Secondary outcome [2] 321406 0
The prevalence of postprandial hypotension in survivors of critical illness that are very elderly (aged > 80 years). (by monitoring blood pressure and heart rate response to ingestion of a 300mL glucaid drink using an automated blood pressure cuff)
Timepoint [2] 321406 0
BP and HR will be assessed 5 minutes before the ingestion of the drink and at 3 min intervals until 240 minutes. This will occur at all three study visits (at 3, 12 and 36 months post discharge from hospital)
Secondary outcome [3] 321448 0
The prevalence of postprandial hypotension in survivors of critical illness that have autonomic dysfunction, diabetes and/or using antihypertensive drugs. This will be determined by self-report by the participant and reviewing the patient's medical records. Blood pressure and heart rate response to ingestion of a 300mL glucaid drink will be measured using an automated blood pressure cuff.
Timepoint [3] 321448 0
BP and HR will be assessed 5 minutes before the ingestion of the drink and at 3 min intervals until 240 minutes. This will occur at all three study visits (at 3, 12 and 36 months post discharge from hospital)
Secondary outcome [4] 321451 0
Falls risk after discharge from intensive care unit (using the Falls Risk for Older People in the Community Screen i.e. FROP-Com Screen)
Timepoint [4] 321451 0
FROP-Com Screen will be conducted 10 minutes prior to ingestion of drink. This will be occur at all three study visits ( at 3, 12, and 36 months)
Secondary outcome [5] 321452 0
The relationship between rapid gastric emptying and postprandial hypotension in elderly survivors of critical illness (gastric emptying will be measured using scintography and breath test while PPH will be assessed by monitoring blood pressure and heart rate response to ingestion of a 300mL glucaid drink using an automated blood pressure cuff)
Timepoint [5] 321452 0
Scintographic gastric emptying curve ( expressed as percentage of maximum content of total stomach) and the total stomach content will be measured at 15 minutes for the first hour and then every minutes thereafter until 240 minutes. From scintography, the lag phase and 50% emptying time will also be obtained to measure gastric emptying.
Breath test will be done at 5 minute intervals for the first hour and then every 15 minutes thereafter till 240 minutes.
BP and HR will be assessed 5 minutes before the ingestion of the drink and at 3 min intervals until 240 minutes.
This occurs at all three study visits (at 3, 12 and 36 months post discharge from hospital).
Secondary outcome [6] 321453 0
serum gastrointestinal hormones (GLP-1 and GIP) prior and following ingestion of drink (using blood samples)
Timepoint [6] 321453 0
Blood samples will be obtained immediately prior to ingestion of the drink and every 15 minutes for the first hour than every 30 minutes for the second hour then hourly until the fourth hour of the study. This will occur at all three study visits ( 3, 12 and 26 months post discharge from hospital)
Secondary outcome [7] 321454 0
symptoms experienced by participants prior and following ingestion of meal (using a visual analogue scale asking patients if they feel tired, dizzy, faint, sick, drowsy, calm, thirsty, weak, chest pain, indigestion and headache)
Timepoint [7] 321454 0
Visual analogue scale will be done immediately prior to ingestion of the drink and then every 15 minutes until 240 minutes. This will occur at all three study visits ( at 3, 12, and 36 months post discharge from hospital).
Secondary outcome [8] 321455 0
Mortality over time (using hospital electronic repositories)
Timepoint [8] 321455 0
Twelve months and three years post hospital discharge
Secondary outcome [9] 321535 0
Sensation of appeptite prior and after ingestion of drink.
Timepoint [9] 321535 0
Visual analogue scale will be done immediately prior to ingestion of the drink and then every 15 minutes until 240 minutes. This will occur at all three study visits ( at 3, 12, and 36 months post discharge from hospital).
Secondary outcome [10] 321537 0
Rehospitalisations over time (using hospital electronic repositories)
Timepoint [10] 321537 0
Twelve months and three years post hospital discharge
Secondary outcome [11] 321539 0
Serum insulin prior and following ingestion of meal. ( using blood samples)
Timepoint [11] 321539 0
Blood samples will be obtained immediately prior to ingestion of the drink and then every 15 minutes for the first hour, then every 30 minutes for the second hour, then hourly until the fourth hour of the study. This will occur at all three study visits ( 3, 12 and 26 months post discharge from hospital)
Secondary outcome [12] 321542 0
Serum catecholamines prior and following ingestion of drink ( using blood samples)
Timepoint [12] 321542 0
Blood samples will be obtained immediately prior to ingestion of the drink and then every 15 minutes for the first hour, then every 30 minutes for the second hou,r then hourly until the fourth hour of the study. This will occur at all three study visits ( 3, 12 and 26 months post discharge from hospital)
Secondary outcome [13] 321543 0
Blood glucose levels prior and following ingestion of meal. ( using blood samples and a glucometer)
Timepoint [13] 321543 0
Blood samples will be obtained immediately prior to ingestion of the drink and then every 15 minutes until 240 minutes. This will occur at all three study visits ( 3, 12 and 36 months post hospital discharge)
Secondary outcome [14] 321544 0
Symptoms of postprandial hypotension after discharge of intensive care unit( using postprandial hypotension symptom questionnaire)
Timepoint [14] 321544 0
Postprandial hypotension symptom questionnaire will be done 10 minutes before ingestion of drink. This will occur at all three visits ( 3, 12 and 36 months post hospital discharge)
Secondary outcome [15] 321545 0
Frailty of patient post intensive care unit discharge ( using Canadian Study on health and ageing clinical frailty scale)
Timepoint [15] 321545 0
This frailty scale will be done 10 minutes prior to ingestion of the drink. This will be repeated at all 3 study visits (3, 12 and 36 months post hospital discharge)
Secondary outcome [16] 321546 0
Quality of life post intensive care unit discharge ( and the EQ-5D-5L questionnaires)
Timepoint [16] 321546 0
EQ-5D-5L will be done 10 minutes prior ingestion of meal. This will be done at all 3 study visits( 3, 12 and 36 months)
Secondary outcome [17] 321549 0
Ability to conduct independent acitivies of daily living post intensive care unit discharge (using the Katz index, Lawtown's instrumental activities of daily living scale)
Timepoint [17] 321549 0
Katz index, lawton's instrumental activities of daily living scale will be done 10 minutes prior ingestion of meal. This will be done at all 3 study visits( 3, 12 and 36 months).

Eligibility
Key inclusion criteria
Patients aged 65 years of age or older and who remain in ICU for > 48 hours. Included patients must all be anticipated to survive critical illness.
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
refusal or unable to obtain informed consent
reside a distance of > 50 km from hospital
it is anticipated the patient will die within 3 months of ICU discharge

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
There are no previous similar studies, but assuming a background rate of 20% in the community and a prevalence in our cohort of 45%, a sample size of 32 patients will provide 90% power to detect this difference (two sided alpha of 0.05).

Given limited existing data, an interim analysis of data from the first ten patients will be performed by an independent statistician.

Outcome variables will be summarised using standard descriptive statistics and analysed by a professional biostatistician. We will report prevalence for the entire cohort as well as a priori subgroups (patients with autonomic neuropathy, diabetes and those taking anti-hypertensives). We will report the relationships between postprandial hypotension and the following outcomes; falls; symptoms; frailty; quality of life; gastric emptying rate; autonomic dysfunction; blood glucose; serum insulin; GLP-1 and GIP; morbidity and mortality.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
9/03/2016
Actual
13/03/2016
Date of last participant enrolment
Anticipated
28/02/2017
Actual
18/10/2016
Date of last data collection
Anticipated
31/12/2017
Actual
9/02/2018
Sample size
Target
32
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 5377 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 12838 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 293031 0
University
Name [1] 293031 0
University of Adelaide
Country [1] 293031 0
Australia
Primary sponsor type
Individual
Name
A/Prof. Adam Deane
Address
ICU Research Department,
Level 4 North Wing, Royal Adelaide Hospital,
North Terrace, Adelaide, SA 5000
Australia
Country
Australia
Secondary sponsor category [1] 291806 0
Individual
Name [1] 291806 0
Miss Thu Anh Ngoc Nguyen
Address [1] 291806 0
ICU Research Department,
Level 4 North Wing, Royal Adelaide Hospital,
North Terrace, Adelaide, SA 5000
Australia
Country [1] 291806 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294542 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 294542 0
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Ethics committee country [1] 294542 0
Australia
Date submitted for ethics approval [1] 294542 0
03/12/2015
Approval date [1] 294542 0
29/01/2016
Ethics approval number [1] 294542 0
HREC/15/RAH/525, Protocol Number: R20151203

Summary
Brief summary
In older persons in the community postprandial hypotension (PPH) is an important clinical problem, being a potent predictor of falls, syncope, coronary events and stroke. Furthermore, the presence of PPH is strongly associated with dying independent of other risk factors.

Older patients that have survived critical illness and been discharged from hospital have a greater mortality rate compared to younger populations. Older survivors of critical illness also experience a greater reduction in physical function post–ICU when compared to younger survivors.

Given the prevalence and impact of PPH in older persons living in the community it is intuitively likely that PPH will occur frequently in survivors of critical illness aged 65 years and older and be associated with adverse outcomes. It is essential to obtain these epidemiological data prior to embarking on a program of work to evaluate potential treatments.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64070 0
A/Prof Adam Deane
Address 64070 0
ICU Research Department,
Level 4 North Wing, Royal Adelaide Hospital,
North Terrace, Adelaide, SA 5000
Country 64070 0
Australia
Phone 64070 0
+61 8 8222 4624
Fax 64070 0
Email 64070 0
[email protected]
Contact person for public queries
Name 64071 0
Thu Anh Ngoc Nguyen
Address 64071 0
ICU Research Department,
Level 4 North Wing, Royal Adelaide Hospital,
North Terrace, Adelaide, SA 5000
Country 64071 0
Australia
Phone 64071 0
+61 8 8222 4624
Fax 64071 0
Email 64071 0
[email protected]
Contact person for scientific queries
Name 64072 0
Thu Anh Ngoc Nguyen
Address 64072 0
ICU Research Department,
Level 4 North Wing, Royal Adelaide Hospital,
North Terrace, Adelaide, SA 5000
Country 64072 0
Australia
Phone 64072 0
+61 8 8222 4624
Fax 64072 0
Email 64072 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Critical Care and Resuscitation (in-press). Accept... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePostprandial hypotension in older survivors of critical illness.2018https://dx.doi.org/10.1016/j.jcrc.2018.01.012
N.B. These documents automatically identified may not have been verified by the study sponsor.