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Chronic Obstructive Pulmonary DiseaseNCT02329522

USCOM For Assessing Patients With COPD

An observational study of Chronic Obstructive Pulmonary Disease, run by Chinese University of Hong Kong at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Objective The Ultrasonic Cardiac Output Monitor (USCOM) is a non-invasive, quantitative method for measuring and monitoring cardiovascular haemodynamic parameters in patients. The aims of this study are: 1. To investigate whether there is any correlation between haemodynamic parameters and COPD severity. 2. Read more about this study

Who is it for?
Ages 40 years and olderHealthy volunteers can take part
Conditions the study is for
Chronic Obstructive Pulmonary Disease
What is being tested?
Ultrasonic Cardiac Output Monitor and Spirometry
Type of treatment
Medical device
How many people
200 participants
Where
1 siteChina
Study dates
Feb 2014to Sep 2020
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Patients with a de novo diagnosis of COPD or a known history of COPD who attend a respiratory clinic or the emergency department in the Prince of Wales Hospital (Shatin, Hong Kong) will be recruited.

Who may be able to join

  • Age >40 years;
  • Clinically diagnosed as COPD by physicians;
  • Obtain any one of exacerbating symptoms (increased dyspnoea, sputum production, sputum volume, wheeze, cough or exertional dyspnoea);

Who cannot join

  • Known or suspected pregnancy, lactating patients, active malignancies, severe mobility problems (e.g. significant painful arthritis), and confusion or dementia .

Trial locations and contacts

1 site in 1 country.

China1 site
  • Prince of Wales Hospital

    Hong Kong

Other trials in China

About this study

Official title: Non-Invasive Doppler Ultrasound For Assessing Patients With Chronic Obstructive Pulmonary Disease: A Prospective Observational Study

Objective

The Ultrasonic Cardiac Output Monitor (USCOM) is a non-invasive, quantitative method for measuring and monitoring cardiovascular haemodynamic parameters in patients. The aims of this study are:

Read more
  1. To investigate whether there is any correlation between haemodynamic parameters and COPD severity.
  2. To investigate whether USCOM-derived haemodynamic variables may be used as prognostic indicators of 6-month, 1-year, 3-year and 5-year readmission.
  3. To investigate whether USCOM-derived haemodynamic variables may be used as prognostic indicators of 6-month, 1-year, 3-year and 5-year all-cause mortality.

Design, Setting and Subjects This prospective observational study will be conducted in the Prince of Wales Hospital in Hong Kong.

Interventions Haemodynamic measurements made using the USCOM, and spirometry, will be performed as appropriate on subjects in respiratory clinic, the emergency department, medical wards and on ICU. In order to assess inter-observer variability, a second, blinded operator will repeated 15% of scans.

Read the detailed description

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the world, a lung disorder which is characterized by a partially reversible airflow limitation, which is usually progressive, and associated with an abnormal inflammatory response to noxious particles or gases. In 2005, among elderly Hong Kong Chinese (age ≥60 years) in Hong Kong with COPD defined as an FEV1/FVC <70%, 19.6% males and 11.9% females suffered from moderate levels of severity.

From an initial stable condition, an acute exacerbation of COPD (AECOPD) is characterized by a sudden onset of breathlessness, purulent sputum, and increases in sputum volume. Other symptoms include increasing cough, wheeze, chest tightness or fatigue. The major cause of AECOPD is infection, although other stimulating factors include air pollution, withdrawal of medication, and low temperature. After the first admission of an exacerbation, the readmission rate for patients with AECOPD is high. The mean number of annual readmissions is 2.2 episodes, with a one-year mortality rate of 14%.

Spirometry can help to diagnose COPD patients, and a post-bronchodilator FEV1/FVC<0.7 confirms the presence of airflow limitation. The classification of severity of airflow limitation in COPD is based on GOLD category. The lower the post-bronchodilator FEV1, the higher is the severity. This method is useful for assessing patients with stable COPD only. For those with AECOPD, this method may not be easy to conduct and assess patients immediately due to patients' difficulty in breathing.

A common dilemma facing clinicians is whether patients presenting with breathlessness, cough and wheeze have an acute exacerbation of COPD, an acute exacerbation of left ventricular failure (LVF), or some degree of both. Making an accurate diagnosis is important as the treatment in each case is different, and a quick recovery depends upon appropriate and timely intervention and treatment.

Unlike acute exacerbations of asthma, there are no objective guidelines on how to assess the severity and prognosis of patients presenting to hospital with acute exacerbations of COPD. However, the CURB65, originally intended for assessing patients with pneumonia, has been evaluated in this context. High CURB65 scores in patients presenting with acute exacerbations of COPD do predict increasing risk of hospital and one month mortality from 2 to 21% but do not predict patients with very high risk.

In healthy subjects, the presence or absence of carbon dioxide retention influences the body's haemodynamic response. Hypercapnia has been shown to increase mean pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), heart rate (HR), stroke volume (SV), cardiac output (CO), and mean arterial BP (MAP). However, hypercapnia does not appear to affect indices of systolic function, such as peak aortic velocity and aortic mean and peak acceleration, or plasma renin, angiotensin II, and aldosterone activity.

In stable patients with compensated COPD, elevations in CO2 trigger central and peripheral chemoreceptors resulting in an increased depth and rate of respiration, bradycardia (via vagal stimulation), and systemic vasoconstriction (via sympathetic stimulation). Therefore, cardiovascular parameters may be either normal or, if there is a degree of carbon dioxide retention resulting in catecholamine release and autonomic stimulation, then moderately hyperdynamic. Patients with COPD should have a cardiac Index (CI), which is elevated either towards the upper half or above the normal range, and may be as high as 5L/min/m2, an elevated SI, an elevated SVR and elevated DO2.

The Smith-Madigan Index II (SMII) is a novel measure of inotropy, which in stable COPD patients should either be normal or, if there are adrenergic effects, then may be elevated to as much as 1.6. The effects of hypercapnia in patients with COPD on potential to kinetic energy ratio (PE/KE, PKR), flow time (FT), peak velocity (Vpk) and mean pressure gradient (Pmn) are unknown.

These changes contrast with patients with acute LVF, where CI is low and the SMII is usually less than 1.0, and commonly around 0.7 - 0.8. PE/KE and SVR are generally much higher, and FT (as a function of SV) is longer. Vpk and Pmn are also lower in LVF.

We have conducted a preliminary study to evaluate the correlation between severity of COPD and haemodynamic parameters. 86 stable COPD patients, 43 AECOPD patients and 36 healthy, age and gender matched subjects were recruited. It was found that the severity of COPD correlated positively with mean heart rate, cardiac index (CI), ejection time percentage (ET%) oxygen delivery index (DO2I) and inotropy. When compared with healthy controls, stable GOLD IV patients had a significantly higher CI (3.98 vs 3.15 l/min/m2, p<0.005), inotropy (2.14 vs 1.72 W/m2, p<0.01) and DO2I (679.8 vs 530.7 ml/min/m2, p<0.01), and a significantly lower potential to kinetic energy ratio (PKR) (43.0 vs 56.6, p<0.05). Moreover, the 30-day readmission rate was the highest in GOPD IV patients. Based on the existing findings, it would be interesting to study the long-term prognostic effect of haemodynamic parameters in COPD patients.

Aim

The aims of the present study for patients visited respiratory clinic or admitted to the Emergency Department (ED), including those admitted to resuscitation room or emergency high dependency unit, are:

  1. To investigate whether there is any correlation between haemodynamic parameters and COPD severity.
  2. To investigate whether USCOM-derived haemodynamic variables may be used as prognostic indicators of 6-month, 1-year, 3-year and 5-year readmission.
  3. To investigate whether USCOM-derived haemodynamic variables may be used as prognostic indicators of 6-month, 1-year, 3-year and 5-year all-cause mortality.

Measurements

  • Haemodynamic measurements using an Ultrasonic Cardiac Output Monitor (USCOM®; USCOM Pty Ltd, NSW, Australia)
  • Lung function assessment using Spirometry (MICROLAB 3300 spirometer; Micro Medical, Kent, UK)
  • 6-minute walk test
  • Borg dyspnoea scale
  • Blood pressure
  • End-tidal CO2

Definition of haemodynamic parameters:

  • Velocity time integral (vti) is the integral of the flow profile, i.e. the distance the blood travels in one beat. The unit of vti is m/s.
  • Cardiac output (CO) is the volume of blood pumped by the heart in one minute: CO = SV x HR. The unit is l/min.
  • Cardiac index (CI) is equal to CO divided by BSA. The unit is l/min/m2.
  • Stroke volume (SV) is the volume of blood ejected from the heart during one systolic stroke. SV = vti x πr2,where πr2 = flow cross sectional area. The unit of SV is ml.
  • Stroke volume index (SVI) is SV divided by BSA and the unit is ml/m2.
  • Stroke volume variation (SVV) is the percentage change in SV between a group of beats. SVV = (SVmax - SVmin x 100) / [(SVmax + SVmin)/2].
  • Systemic vascular resistance (SVR) is the pressure against which the heart pumps. SVR = MAP/CO. The unit is d.s.cm-5.
  • Systemic vascular resistance index (SVRI) SVRI = SVR x BSA d.s.cm-5m2.
  • Oxygen delivery (DO2) is calculated by the equation: DO2 = 1.34 x Hb x SpO2/100 x CO, where Hb = hemoglobin in grams of hemoglobin per litre of blood (g/l); SpO2 = the peripheral oxygen saturation as a percentage (%). The unit of DO2 is ml/min.
  • Oxygen delivery index (DO2I) is equal to DO2 divided by BSA. The unit of DO2I is ml/min/m2.
  • Inotropy index refers to (Potential energy + Kinetic energy) divided by body surface area. The unit of inotropy is W/m2.
  • Potential to kinetic energy ratio (PKR) is the energy used to produce blood pressure divided by the energy used to produce blood flow.
Being tested
Ultrasonic Cardiac Output Monitor, Spirometry
Keywords
Haemodynamics, Chronic obstructive pulmonary disease, Ultrasonic Cardiac Output Monitor, severity
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ultrasonic Cardiac Output MonitorDevice

    Also called USCOM

    An Ultrasonic Cardiac Output Monitor (USCOM; USCOM Pty Ltd, NSW, Australia) is a non-invasive Doppler ultrasonography. It is capable of measuring haemodynamic parameters non-invasively and appears to be simple and rapid to use, portable, relatively inexpensive and has less potential complications compared with the standard technique, pulmonary artery thermodilution (PATD).

    USCOM scans will be performed on patients to measure direct and derived haemodynamic variables, which will be performed in the supine position wherever possible. A transducer will be placed on the chest in either the suprasternal position to measure trans-aortic blood flow, or the left parasternal position to measure transpulmonary blood flow.

  • SpirometryDevice

    Also called Lung function test

    Spirometry assesses lung function through measuring the amount (volume) and/or speed (flow) of air that can be inhaled and exhaled. Patients are regarded as COPD if their Forced expiratory volume in 1 second (FEV1) to Forced vital capacity (FVC) ratio are smaller than 70%. Patients were required to perform three blowing manoeuvres, and post-bronchodilator test results were obtained within 20 minutes to 4 hours after inhaling 400 mg of salbultamol.

Study groups in NCT02329522
Study groupRoleWhat they receive
Stable COPD patientsPatients will be assessed using USCOM and spirometry. For those with FEV1 to FVC ratio smaller than 70%, they will be classified as COPD.
Receives: Device: Ultrasonic Cardiac Output Monitor; Device: Spirometry
AECOPD patientsPatients will be assessed using USCOM and spirometry. Spirometry will be assessed after 2 to 4 weeks post-hospital discharge.
Receives: Device: Ultrasonic Cardiac Output Monitor; Device: Spirometry
Patient ControlsPatients will be assessed using USCOM and spirometry. For those with COPD symptoms but FEV1 to FVC ratio greater than 70%, they will be classified as non-COPD.
Receives: Device: Ultrasonic Cardiac Output Monitor; Device: Spirometry
Healthy ControlsHealthy subjects, with no history of COPD or other significant chronic illness will be recruited as healthy controls. Subjects will be matched for age and gender with the patient groups. They will be assessed using USCOM.
Receives: Device: Ultrasonic Cardiac Output Monitor

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The difference in mean cardiac index (CI) among the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I, II, III, IV and healthy subjects.

    Measured: On Day 1

Secondary outcomes (5)
  1. The difference in velocity time interval (vti) obtained using USCOM among GOLD stage I, II, III, IV and healthy subjects

    USCOM - Ultrasonic Cardiac Output Monitor Please see the definition of the haemodynamic parameters in Detailed Description.

    Measured: On Day 1

  2. The differences in USCOM-derived haemodynamic parameters, including CO, SV, SVI, SVV, SVR, SVRI, DO2, DO2I, Intropy and PKR obtained using USCOM among GOLD stage I, II, III, IV and healthy subjects

    Please see the definition of the haemodynamic parameters in Detailed Description.

    Abbreviation: cardiac output (CO), stroke volume (SV), stroke volume index (SVI), stroke volume variation (SVV), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), oxygen delivery (DO2), oxygen delivery index (DO2I), Intropy and potential to kinetic energy ratio (PKR)

    Measured: On Day 1

  3. The differences in USCOM-derived haemodynamic parameters, including CO, CI, SVR, SVRI, SVV, DO2, DO2I, Intropy and PKR between stable and acute exacerbated condition

    Please see the definition of the haemodynamic parameters in Detailed Description.

    Abbreviation: cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), stoke volume variation (SVV), oxygen delivery (DO2), oxygen delivery index (DO2I), Intropy and potential to kinetic energy ratio (PKR).

    Measured: On Day 1

  4. The number of 6-month, 1-year, 3-year and 5-year readmission in COPD patients

    Measured: Year 5

  5. The number of 6-month, 1-year, 3-year and 5-year all-cause mortality in COPD patients

    Measured: Year 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Dec 2014 (estimated)
  2. Study startFeb 2014
  3. Primary completionOct 2014
  4. Study completionSep 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02329522
Sponsor's protocol ID
2013.640
Status last verified
Sep 2017
First submitted
22 Dec 2014
Last updated
2 Oct 2017
Results posted
No
Data monitoring committee
No

Publications

  • Ko FW, Woo J, Tam W, Lai CK, Ngai J, Kwok T, Hui DS. Prevalence and risk factors of airflow obstruction in an elderly Chinese population. Eur Respir J. 2008 Dec;32(6):1472-8. doi: 10.1183/09031936.00058708. Epub 2008 Aug 6.

    PubMed 18684847
  • Wedzicha JA. Role of viruses in exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2004;1(2):115-20. doi: 10.1513/pats.2306030.

    PubMed 16113423
  • Anderson HR, Spix C, Medina S, Schouten JP, Castellsague J, Rossi G, Zmirou D, Touloumi G, Wojtyniak B, Ponka A, Bacharova L, Schwartz J, Katsouyanni K. Air pollution and daily admissions for chronic obstructive pulmonary disease in 6 European cities: results from the APHEA project. Eur Respir J. 1997 May;10(5):1064-71. doi: 10.1183/09031936.97.10051064.

    PubMed 9163648
  • Wouters EF, Postma DS, Fokkens B, Hop WC, Prins J, Kuipers AF, Pasma HR, Hensing CA, Creutzberg EC; COSMIC (COPD and Seretide: a Multi-Center Intervention and Characterization) Study Group. Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: a randomised controlled trial. Thorax. 2005 Jun;60(6):480-7. doi: 10.1136/thx.2004.034280.

    PubMed 15923248
  • Donaldson GC, Seemungal T, Jeffries DJ, Wedzicha JA. Effect of temperature on lung function and symptoms in chronic obstructive pulmonary disease. Eur Respir J. 1999 Apr;13(4):844-9. doi: 10.1034/j.1399-3003.1999.13d25.x.

    PubMed 10362051
  • Osman IM, Godden DJ, Friend JA, Legge JS, Douglas JG. Quality of life and hospital re-admission in patients with chronic obstructive pulmonary disease. Thorax. 1997 Jan;52(1):67-71. doi: 10.1136/thx.52.1.67.

    PubMed 9039248
  • Ko FW, Ng TK, Li TS, Fok JP, Chan MC, Wu AK, Hui DS. Sputum bacteriology in patients with acute exacerbations of COPD in Hong Kong. Respir Med. 2005 Apr;99(4):454-60. doi: 10.1016/j.rmed.2004.09.011.

    PubMed 15763452
  • Chang CL, Sullivan GD, Karalus NC, Mills GD, McLachlan JD, Hancox RJ. Predicting early mortality in acute exacerbation of chronic obstructive pulmonary disease using the CURB65 score. Respirology. 2011 Jan;16(1):146-51. doi: 10.1111/j.1440-1843.2010.01866.x.

    PubMed 20920140
  • Kiely DG, Cargill RI, Lipworth BJ. Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans. Chest. 1996 May;109(5):1215-21. doi: 10.1378/chest.109.5.1215.

    PubMed 8625670
  • Smith BE, Madigan VM. Non-invasive method for rapid bedside estimation of inotropy: theory and preliminary clinical validation. Br J Anaesth. 2013 Oct;111(4):580-8. doi: 10.1093/bja/aet118. Epub 2013 May 3.

    PubMed 23645929

Questions about this trial

What is this clinical trial studying?

An observational study of Chronic Obstructive Pulmonary Disease, run by Chinese University of Hong Kong at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The difference in mean cardiac index (CI) among the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I, II, III, IV and healthy subjects. (time frame: On Day 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02329522, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2017.

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