ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12612001300864

Ethics application status

Approved

Date submitted

30/11/2012

Date registered

17/12/2012

Date last updated

17/12/2012

Type of registration

Prospectively registered

Titles & IDs

Public title

Development of an Effective Treatment for Cheyne-Stokes Respiration

Scientific title

The effect of inspired carbon dioxide on Cheyne Stokes Respiration in Heart Failure Patients

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Cheyne-Stokes Respiration

Condition category

Condition code

Respiratory

Sleep apnoea

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Each patient will be randomised on the first night of study to receive treatment with either 1-3% carbon dioxide or air. At the start of the night, the starting condition is that the patient will breathe from a circuit delivering air via a Douglas bag. The circuit will contain a 4-way Hans-Rudolph valve so that the patient can be switched rapidly to the test gas as desired. Once the first apnea is evident from the patient's ventilatory airflow signal, and from mask pressure and abdominal and chest respibands, the valve will be switched to a circuit delivering the test gas via another Douglas bag. The test gas will be continued for 10 minutes before the valve will be used to switch the patient back to the air supply. On the appearance of another apnea the valve will be used to switch the patient to the test gas for a further 10 minutes. This process will be repeated for the entire study night.
One week or more following the first arm of the study, the patient will enter the second arm in which the alternate test gas will be applied for 10 minutes once an apnea is observed. Patients will be studied as soon as practicable following the on e week washout period with a maximum of four weeks between studies.

Intervention code [1]

Treatment: Other

Comparator / control treatment

The patient will breathe air as the standard inspired gas throughout the study, but will switch to the intervention ( 1-3% carbon dioxide or air) whenever an apnoea is observed. The intervention will then continue for periods of 10 minutes, followed by a return to air until the next apnea is observed when once again the intervention gas will be switched on. The exposure to the intervention will depend upon the frequency of apnea during the night.

Control group

Placebo

Outcomes

Primary outcome [1]

Cessation of Cheyne-Stokes Respiration as measured by reduction in central apnoea index and central apnoea-hypopnoea index during the study period.

Timepoint [1]

Measured at time of intervention

Primary outcome [2]

Change in apnoea index and apnoea-hypopnea index (as defined by American Academy of Sleep Medicine(AASM)).

Timepoint [2]

Measured across total sleep time of study

Primary outcome [3]

Improvement in sleep architecture as measured by total sleep, percentage slow wave sleep and percentage rapid eye movement sleep as measured during the sleep study using AASM criteria.

Timepoint [3]

Measured across total sleep time of study

Secondary outcome [1]

pro-brain natriuretic peptide in blood

Timepoint [1]

measured at start of night of study and in the morning

Secondary outcome [2]

markers of inflammation including Urine analysis for Catecholamines (Epinephrine, Norepinephrine and Dopamine), Creatinine and renal electrolytes - Na, K, Cl, BUN, uric acid. Serum or Plasma analysis for NTpro-BNP, Troponin I and C-Reactive Protein, ST2, IL-6, cystatin C, hs-CRP, galectin-3, copeptin, sIL-6R, IL-18, and TNFalpha.

Timepoint [2]

measured at start of night of study and in the morning

Secondary outcome [3]

work of breathing as calculated conventionally using the Campbell diagram

Timepoint [3]

Measured across total sleep time in the study

Eligibility

Key inclusion criteria

Heart failure as measured by an ejection fraction <45%
able to provide informed consent

Minimum age

35 Years

Maximum age

100 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Patients will be excluded unless their lung function is >70% predicted. Patients will be stable, with no hospitalisation over the preceding 4 weeks. Exclusion criteria will include significant renal, neurologic or respiratory disease.
The patients are required to be in a stable health condition with no changes in treatment between the study nights.

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)

Patients referred by their doctors for routine polysomnography will be made aware of the study on their first contact, either by phone or in person, with the sleep physician. On the day of their diagnostic sleep study, patients have a lung function assessment made during the afternoon. At that time, they will have the study explained to them, they will be provided with a Patient Information and Consent Form to read, and they will be invited to participate. Any questions they have about the study will be answered.

Allocation will be concealed from the patient and those analysing the data. It will not be concealed from those performing the randomisation who will also implement the selected intervention on the night of the studies. Administration of air versus carbon dioxide will be performed from an adjoining room with the patient unaware of the provided gas.

People assessing and analysing data will not be told of the intervention provided during each individual study.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Order of treatment (sham or carbon dioxide) is randomised for each patient with the toss of a coin.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Crossover

Other design features

None

Phase

Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/01/2013

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)

VIC

Recruitment hospital [1]

The Alfred - Prahran

Recruitment hospital [2]

Monash Medical Centre - Clayton campus - Clayton

Recruitment postcode(s) [1]

3004

Recruitment postcode(s) [2]

3168

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

GPO Box 1421
Canberra
ACT 2601

Country [1]

Australia

Primary sponsor type

Individual

Name

Dr Philip Berger

Address

Ritchie Centre
Level 5, Block B
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Professor Matthew Naughton

Address [1]

Department of Allergy, Immunology and Respiratory Medicine
The Alfred
Commercial Road
Melbourne
Victoria 3004

Country [1]

Australia

Other collaborator category [1]

Individual

Name [1]

Dr Garrun Hamilton

Address [1]

Department Respiratory and Sleep Medicine
Level 2, Block B
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Health Human research and Ethics Committee

Ethics committee address [1]

Level 4
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

11/02/2012

Approval date [1]

11/04/2012

Ethics approval number [1]

12031B

Ethics committee name [2]

The Alfred Hospital human Research and Ethics Committee

Ethics committee address [2]

Alfred Health
55 Commercial Road
Melbourne
Victoria 3004

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

11/04/2012

Ethics approval number [2]

44/12

Summary

Brief summary

As many as half of all patients with heart failure exhibit Cheyne-Stokes respiration (CSR), a form of disordered breathing in which short periods (approx 30 sec) of regular breathing alternate with periods during which breathing stops (apnea). Patients with heart failure and CSR have a markedly poorer outcome compared to heart failure patients whose breathing is normal during sleep. While the reasons for the differential outcome are not fully known, it is likely that the direct consequences of CSR, which include increased sympathetic activity and frequent declines in blood oxygen level, contribute to impairment of cardiac function. When effective treatment causes CSR to revert to a continuous breathing pattern, the available evidence shows that patient condition and survival improve. However, the current front-line therapy, continuous positive airway pressure (CPAP) ameliorates CSR in only 50% of heart failure patients. We plan to use a novel loop gain theory developed in our laboratory that enables us to calculate a precise level of inspired CO2 for each patient that will convert CSR into a continuous pattern. 

The work planned in this program will employ a manual method to deliver an optimised CO2 treatment for each patient during the night whenever the patient begins to exhibit CSR. In order to carry out our study, we will recruit patients with heart failure and suspected CSR for overnight sleep studies which involve measurement of respiratory, cardiovascular and sleep variables. Based upon our studies over the past two years in such patients, carried out at the Alfred and Monash Medical Centre, CO2 treatment will restore continuous breathing in all patients. In the current study we will determine how termination of CSR affects patients in terms of respiratory and cardiovascular function, as well as sleep architecture and quality (duration of sleep and time in its various stages). We anticipate that our proposed study will show that restricting the time a patient spends breathing with a periodic pattern while asleep will provide an acute benefit and justify a major program of device development to translate our technique into a home-based device for overnight patient use. Success in our program has the potential to benefit many of the approximately 25 million people world-wide with congestive heart failure, a condition that remains one of the leading causes of morbidity and mortality in the western world and now constitutes the leading cause of hospitalisation in developed countries.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Philip Berger

Address

Ritchie Centre
Level 5, Block B
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168

Country

Australia

Phone

+61395945477

Fax

+61395946811

philip.berger@monash.edu

Contact person for public queries

Name

Elizabeth Skuza

Address

Ritchie Centre
Level 5, Block B
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168

Country

Australia

Phone

+61395945398

Fax

+61395946811

elizabeth.skuza@monash.edu

Contact person for scientific queries

Name

Philip Berger

Address

Ritchie Centre
Level 5, Block B
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168

Country

Australia

Phone

+61395945477

Fax

+61395946811

philip.berger@monash.edu

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

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically