ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12619001260112

Ethics application status

Approved

Date submitted

9/08/2019

Date registered

11/09/2019

Date last updated

16/12/2020

Date data sharing statement initially provided

11/09/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Malignant Hyperthermia - A new simple diagnostic test

Scientific title

Assessing Calcium flux in single muscle fibres in response to halothane and caffeine to diagnose Malignant Hyperthermia.

Secondary ID [1]

Nil Known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Malignant Hyperthermia

Condition category

Condition code

Anaesthesiology

Anaesthetics

Intervention/exposure

Study type

Observational

Patient registry

True

Target follow-up duration

Target follow-up type

Weeks

Description of intervention(s) / exposure

Malignant Hyperthermia (MH) is a potentially life threatening event in response to anaesthetic triggering agents – volatile anaesthetics or depolarising muscle relaxants, resulting from alterations in intracellular calcium homeostasis of skeletal muscle cells.
Current diagnosis of MH involves a functional test on a large skeletal muscle biopsy from the leg, obtained under a non-triggering general anaesthetic - the in-vitro contracture test (IVCT). A diagnosis of MH susceptible is determined at a critical threshold of 0.2 g of force at 2 mM or less of caffeine and 2% or less of halothane in each test.

This study will assess intracellular calcium movements in isolated skeletal muscle fibres, to diagnose MH. Force is not used as a measure of responsiveness to RYR1 agonists. In single muscle fibre testing, the Ca2+ waves induced by caffeine or halothane imaged by confocal microscopy are classified by their amplitude and frequency. The amplitude is typically an indicator of the amount of Ca2+ being released through the RyR1s; and the frequency of the waves is indicative of the susceptibility of the RyR1 to opening in the presence of agonist.

Individual testing will occur over 3 hours. Results from the IVCT and the single muscle fibre assay will be collated. Direct comparison of the results will establish the reliability of the new technique, with reference to the current IVCT. We will calculate the proportion of these where the two methods give identical categorization as negative or susceptible using the Wilson method. If 200 out of 200 patients are categorized identically by the two methods then the 95% CI will be 0.981 to 1.00, meaning that the level of disagreement is no more than 1.2%. Recruitment of 200 samples will occur over a two year period.

Intervention code [1]

Diagnosis / Prognosis

Comparator / control treatment

Control : the current diagnostic in vitro contracture test (IVCT)

Control group

Active

Outcomes

Primary outcome [1]

To confirm that single muscle fibre testing can be used to diagnose Malignant Hyperthermia. This would be assessed by comparison with the IVCT, the current "gold standard" for MH diagnosis.

Timepoint [1]

2 years post commencement of study will allow recruitment of 200 participants. Based on discussions with the senior hospital statistician 200 comparable tests will confirm the reliability of the single muscle fibre test.

Secondary outcome [1]

Five hundred potential malignant hyperthermia susceptible patients appropriately diagnosed as assessed by intracellular calcium movements in isolated skeletal muscle fibres.

Timepoint [1]

5 years. We anticipate that any diagnostic errors or complications of the new diagnostic test would become apparent within 5 years of the commencement of the study.

Eligibility

Key inclusion criteria

Patients who have experienced a MH clinical episode or their relatives have MH susceptibility, or they do not carry the diagnostic family genetic pathogenic variant. These patients display no clinical signs of neuromuscular disease.

Minimum age

18 Years

Maximum age

79 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Children will be excluded

Study design

Purpose

Screening

Duration

Cross-sectional

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/11/2019

Actual

10/03/2020

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

200

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,VIC

Recruitment hospital [1]

The Children's Hospital at Westmead - Westmead

Recruitment hospital [2]

Royal Melbourne Hospital - City campus - Parkville

Recruitment postcode(s) [1]

2145 - Westmead

Recruitment postcode(s) [2]

3050 - Parkville

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

The Pickles Foundation

Address [1]

P O Box 428
KILLARA NSW 2017

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Australian & New Zealand College of Anaesthetists

Address [2]

ANZCA House
630 St Kilda Road
Melbourne VIC 3004
Australia

Country [2]

Australia

Primary sponsor type

Individual

Name

Dr Margaret Perry

Address

The Malignant Hyperthermia Unit, Sydney
Anaesthetic Department
The Children's Hospital, Westmead
Locked Bag 4001 Westmead NSW 2145

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Dr Robyn Gillies

Address [1]

The Malignant Hyperthermia Unit, Melbourne
Anaesthetic Department
Royal Melbourne Hospital
300 Grattan Street (corner of Royal Parade)
Parkville, Victoria 3050

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Sydney Children's Hospitals Network Human Research Ethics Committee

Ethics committee address [1]

Corner Hawkesbury Road and Hainsworth Street
Locked Bag 4001
Westmead NSW 2145

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

01/07/2019

Ethics approval number [1]

2019/ETH08726

Summary

Brief summary

Title:  Malignant Hyperthermia - A new simple diagnostic test 

Malignant Hyperthermia is a life threatening uncommon complication associated with having an anaesthetic. It may be passed down through families from one generation to the next. Many people at risk of Malignant Hyperthermia may be confirmed by a simple genetic test. However all other patients require a sample of muscle (muscle biopsy) taken from the leg, to have special functional testing to confirm they are at risk of Malignant Hyperthermia – the in-vitro contracture test (IVCT). The muscle biopsy is taken from the leg, requiring a surgical operation and a general anaesthetic that is known to be safe with MH.

Technical advancements have enabled the design of a new test on a very small component of the muscle obtained from a minor needle biopsy, under local anaesthetic. Through this project we will show this simple less invasive technique is a reliable test to determine a patient’s potential risk of malignant hyperthermia.

On the east coast of Australia, we have two Malignant Hyperthermia testing units. The Malignant Hyperthermia Units at The Royal Melbourne Hospital (RMH), Victoria and The Children’s Hospital, Westmead, NSW have been established for more than 15 years, and offer assessment of malignant hyperthermia risk through consultation, the muscle biopsy test and genetic analysis. The Muscle Research Laboratory, The University of Queensland, has extensive experience and understanding of skeletal muscle functioning. We will combine the excellence of all departments to improve our understanding of malignant hyperthermia and develop this simple, cheaper less invasive testing for malignant hyperthermia risk.

This study will have implications for providing a clear diagnosis for patients at risk of malignant hyperthermia, while being significantly less invasive than the current muscle biopsy test. A simple investigation acceptable to the general population will increase the number of patients agreeing to define their risk of malignant hyperthermia and thus contribute to safer anaesthesia for our community.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Margaret Perry

Address

The Malignant Hyperthermia Unit
Anaesthetic Department
The Children's Hospital, Westmead
Locked Bag 4001
Westmead, 2145 Sydney NSW

Country

Australia

Phone

+61 2 98452367

Fax

margaret.perry@health.nsw.gov.au

Contact person for public queries

Name

Margaret Perry

Address

The Malignant Hyperthermia Unit
Anaesthetic Department
The Children's Hospital, Westmead
Locked Bag 4001
Westmead, 2145 Sydney NSW

Country

Australia

Phone

+61 2 98452367

Fax

margaret.perry@health.nsw.gov.au

Contact person for scientific queries

Name

Margaret Perry

Address

The Malignant Hyperthermia Unit
Anaesthetic Department
The Children's Hospital, Westmead
Locked Bag 4001
Westmead, 2145 Sydney NSW

Country

Australia

Phone

+61 2 98452367

Fax

margaret.perry@health.nsw.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Not supported by the Ethics approval

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
3948	Study protocol			margaret.perry@health.nsw.gov.au

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

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