TOBI TRIAL INFO

[Guest guest]

What do you think, have a read and tell me your opinions thanks

-----

Subject: BAL Study, Info

> Hi ,

>

>

> The study is looking at the bronchoscopy directed care versus our

> traditional " best quess " therapy. It is a multicentre study ,5 centres in

> Australia and Starship, and children must be enrolled before or at 6

months

> of age. Should a child be randomised to the Bronchoscopy Arm it involves

one

> bronchoscopy before the Babe is/or at 6mths of age and thereafter usual

> treatment. If the baby ever requires a Hospital admission, between 0 to

> 5yrs, related to a respiratory exacerbation which has not responded to the

> standard course of antibiotics, then we do a bronchoscopy and lavage and

> treat specifically for what may be cultured from the Childs lungs. If

> pseudomonas is found they are treated with nebulised TOBI.( High strength

> Tobramycin.)

>

> If the chid is randomised to the non bronchoscopy arm, they have the same

> treatment that we would normally give. However should they have a positive

> culture to pseudomonas from a cough swab etc. they will be treated with

> nebulised TOBI. If at any time it is clinically necessary for this child

to

> have a Bronchoscopy this will be carried out,( with Parental consent)

> regardless of which arm of the study they may be on. At the end of the

Study

> these children will have a Bronchoscopy and Lavage.

>

> All Study participants require 3 mthly medical checks. These are divided

> between your home Paediatrician and the Starship CF Team. Frequency of

> visits to Starship may vary, definitely at the enrolment, and thereafter

at

> least once a year, usually at the time of the child's annual review. We do

> fit this around the individual child and family and if there is a need

they

> are seen more frequently at Starship CF Clinic. We aim to combine most

> routine checks with the child's usual CF Clinic visits and the child's

home

> Paediatrician continues at all times to care for your child. Participants

in

> this Study may chose to leave the Study at any time.

>

> > Thank you for your interest regardless of the outcome of your review of

the

> study. It is always a difficult time following a diagnosis of CF to get to

> grips with everything and all the different treatments that are available,

> and what may be best for Liam, and particularly as you and Shaun have

> already been through a very sad time with your first little baby.

> Understandably you already have concerns regarding the possibility of Liam

> contacting pseudomonas and of the outcomes of any CF treatment options.

>Australasian Cystic Fibrosis Bronchoalveolar Lavage Study.

(BAL)

This study is a multi-centre, randomised; controlled trial of BAL directed

therapy in young children with Cystic Fibrosis being carried out in New

Zealand and Australia. The New Zealand trial is through the Auckland

University and the Study Centre is at Starship Children's Hospital,

Auckland, the Principal Investigator Dr Cass Byrnes, Senior Lecturer and

Honorary Consultant Paediatric Respiratory Department.

The Australian Study Centres are Royal Children's Hospital and Mater

Hospital, Queensland. New Children's Hospital and Hunter Hospital, New

south Wales. Royal Children's Hospital , and Women and Children's

Hospital South Australia.

Many children with Cystic Fibrosis have repeated episodes of chest infection

that often start very early in the child's life and can lead to lung damage.

These infections are not always associated with cough, colds or wheeze so

may be difficult to detect. A way of identifying and monitoring these

infections is by testing the mucus from the lungs. In young children,

toddlers and babies, this is difficult because they cannot cough up the

mucus to be examined and they cannot undergo Lung function test (Breathing

tests) as can an older child.

They can have a cough or throat swab taken but they may have different bugs

in their lungs to their throats. A way to identify these infections in young

children is by seeing the airways and by testing the mucus from the lungs.

This is a Bronchoscopy and Lavage, (BAL).

Recently it is suggested that using this more focused method, (BAL) may be

helpful in preventing the development of harmful lung infections and lung

damage. This may in turn lead to an improved quality of life. We cannot

tell whether this is helpful without performing a trial that compares a

group of young children who are given the standard approach to monitoring

and treatment as per the Standard Cystic Fibrosis Treatment protocol, with a

group given a more intensive monitoring based on flexible bronchoscopy. At

this time there is no strong evidence that your child is likely to do better

or worse with either of these approaches. To be eligible for this trial,

enrolment must be before 6mths of age and infants will be allocated to one

of the two treatment groups by chance alone.

BAL STUDY.

To clarify:

All accommodation and travel cost will be covered by Study.

If a baby should go into this Study the Baby's own Paediatrician will at all

times continue to care for, and manage the care for that child and they will

share the care with the Study Personnel.

The Study is randomized to " Two Arms. "

Arm A, standard care. This Baby will receive the usual treatment according

to the standard Protocol for treatment of children with CF. On enrollment,

the child on this arm receives a baseline medical check before 6mths of age

but does not have a Bronchoscopy and lavage. Every three months routine

medical checks will be carried out by babes own " home " Paediatrician, and

check forms sent to the Study center. Every 12 months babies will have

annual review around the birthdates, their own Paediatricians will perform

this, fill out the check form, send to centre.

If there is an exacerbation of the child's condition and they require a

hospital admission they will be treated according to the Standard Protocol

for treatment of CF children with an exacerbation, IV antibiotics etc.

If pseudomonas is found from a cough swab, once discharged, they will have

2mths of nebulised TOBI medication at home. TOBI medication will be provided

from the Study, no cost involved. This will be the only new addition to the

already standard treatment.

At the end of this Study or at age 5yrs, a Bronchoscopy and Lavage (BAL)

will be performed. This will be the only BAL carried out on this child.

Unless:

During the course of the Study a Bronchoscopy and lavage was considered to

be medically necessary for their medical wellbeing, and this would be the

case, regardless if the child was enrolled in the Study or not.

Arm B: Bronchoscopy Group. Baby randomized to this arm will have a baseline

Medical check, can be by own " home " Paediatrician. and a baseline

Bronchoscopy and Lavage, at Starship children's Hospital, befor 6mths of

age. Every three months routine medical checks will be carried out by babes

own " home " Paediatrician, and check forms sent to the Study center. Every

12 months babies will have annual review around the birthdates, their own

Paediatricians will perform this, fill out the check form, send to Study

centre.

If there is an exacerbation of the child's condition and they require a

hospital admission they will be treated according to the Standard Protocol

for treatment of CF children with an exacerbation, IV antibiotics etc. and

additionally they will have a Bronchoscopy and Lavage.

If pseudomonas is identified, once discharged, they will have 2mths of

nebulised TOBI medication at home. TOBI medication will be provided from the

Study, no cost involved.

At the end of this study or at 5yrs of age the child will have a

Bronchoscopy and Lavage performed.

TOBI Medication is now registered in New Zealand for use of 6yrs and above,

the Study has permission to use it for under 6yrs of age. At this time the

only TOBI medication available for Paediatric use in New Zealand is through

the BAL Study.

Should you come to Starship, Dr Cass Byrnes and I look forward to meeting

you all. Once again many thanks and hoping everything goes well for your

Family.

Kindest Regards,

Merrin Harger,

BAL Study, Project Manager.

> Merrin Harger

> Project Manager, BAL Study

> Division of Paediatrics

> Faculty of Medicine and Health Sciences

> University of Auckland

> New Zealand

> m.harger@...

PARENT INFORMATION SHEET

Version 2. 07/02/2001

A Multi-Centre, Randomised, Controlled Trial of BAL Directed

Therapy in Young Children with Cystic Fibrosis.

This study has received ethical approval from the Auckland Ethics Committee.

Introduction:

You are invited to be part of a study to see which is the better way at

directing the treatment of chest infections for your child.

1. Having wash samples of the airway taken and directing treatment against

the bugs that are grown

2. Estimating which bugs are likely to be causing the problem and treating

without taking airway wash samples.

Background:

You will now know that children with cystic fibrosis (CF) have repeated

episodes of chest infection that can lead to lung damage. These infections

often start very early in life and are not always associated with obvious

symptoms such as cough or wheeze so may be difficult to detect. Lung

infections are usually due to particular bugs. The most common are

Pseudomonas and Staphylococcus. Pseudomonas is found more often as a child

gets older and is associated with more chest infections and more

inflammation in the lungs. The infection and inflammation contributes to

further lung damage. In older children it is easier to monitor the course of

lung disease. Lung function (breathing test) can be measured and any coughed

up mucus can be examined for bugs such as Pseudomonas. In young children

monitoring lung disease is more difficult because neither of these tests can

be done, and bugs grown from throat swabs do not reflect infection that is

in the chest.

Bronchoscopy and Lavage:

Recently it is suggested that using more focused methods of diagnosing chest

infections may be helpful in preventing the development of harmful lung

infections. Many cystic fibrosis centres are now using flexible bronchoscopy

and lavage (BAL) to look for lung infections in young children. Bronchoscopy

involves a long flexible tube being passed into the lungs while the child is

asleep under a general anaesthetic. The main lung airways can be seen and a

sample of mucus from the lungs can be obtained. Lavage is when a sample of

saline is flushed into the lung and then suctioned out and sent for growth

of any bacteria and viruses.

Bronchoscopy is a safe procedure that has been widely used in young

children. All the consultants in the study are experienced in the use of

this technique. Possible side effects are that some children may develop a

fever or increased cough in the first few days after a bronchoscopy is done.

It involves a general anaesthetic and experienced paediatric anaesthetists

at the Starship Hospital will be involved.

Comparison study:

We cannot tell whether doing bronchoscopies is helpful without performing a

trial that compares a group of children given the standard approach to

monitoring and treatment with a group given more intensive monitoring based

on flexible bronchoscopy. At this time we have no strong evidence that your

child is likely to do better or worse with either of these approaches.

Infants will be allocated to one of the two treatment groups by chance

alone.

Usual Treatment Group:

If your child is allocated to standard treatment they will receive treatment

according to strict guidelines. Every time there are respiratory symptoms

such as cough or wheeze or symptoms of a cold, a two-week course of oral

antibiotics will be used. After two weeks your child will be reviewed at the

CF clinic. If the cough is completely better, antibiotics will stop. If the

cough has improved but not completely better, antibiotics will continue for

a further two weeks. Again your child will need to be reviewed at the CF

clinic.

If the cough has not cleared at the end of four weeks of antibiotics or your

child has worsened at any stage then intravenous antibiotics in hospital

will be required. Cough swabs will be taken and if Pseudomonas is found,

your child will receive intravenous antibiotics for two weeks or until

symptoms have improved. This will also be followed by two months of inhaled

antibiotics, TOBI, at home, this will be the only new addition to the

already standard treatment.

Bronchoscopy Group:

If your child is allocated to the bronchoscopy group, flexible bronchoscopy

and BAL will be used to diagnose infection and inflammation in the lungs.

The first bronchoscopy and BAL will be performed close to diagnosis (less

than six months of age). Further bronchoscopies will be done if your child

needs to come into hospital for treatment of a chest infection that has not

settled on oral antibiotic treatment at home. Children with no Pseudomonas

in BAL fluid will continued appropriate oral antibiotic treatment until

symptoms have been resolved. If there is Pseudomonas in the BAL fluid these

children will receive a two-week course of intravenous antibiotics in

hospital, followed by two months of inhaled antibiotics, TOBI, at home. This

is aimed at completely clearing the known infection.

There will be a further BAL taken at the end of the whole (hospital and

home) course of treatment. If there is still Pseudomonas in the BAL your

child will have a further intensive two weeks of intravenous antibiotics and

then two months of inhaled antibiotics. A BAL will again be taken and if

Pseudomonas is still found then we will consider your child to have chronic

colonisation with Pseudomonas that we cannot clear up. If this occurs then

treatment will be according to symptoms and antibiotics will be used with

infections without the need for further bronchoscopies.

Sites and Samples:

This study will be undertaken in young children diagnosed with CF through

the neonatal screening programmes in Queensland, NSW, , South

Australia, and Auckland and Northland, New Zealand. A small amount of the

lavage samples taken at bronchoscopies will be measured for inflammation

factors in Melbourne Australia.

Inaled antibiotic against pseudomonas - TOBI:

TOBI, is a new preparation of a drug called Tobramycin that has been used

for many years both intravenously and nebulised in children. This new

formulation has been developed for the nebuliser and means much higher doses

can be used. TOBI is registered in New Zealand for use 6yrs and above and

it has been approved in the USA, United Kingdom, Europe and Australia.

Although safe in children with CF, it has not been used widely in very young

children. We will therefore need to check for side effects. The amount of

drug absorbed into the bloodstream is considerably less from the nebulised

preparation than the intravenous use preparation that is regularly used.

However we will do hearing tests and a small blood test before and after

having the first course of TOBI and on a yearly basis with the usual yearly

check up.

When the study is over TOBI will not necessarily be available.

At 5 years of age:

The major differences between the two groups will be measured at age five

years when all children regardless of treatment group will have:

? lung function measured

? flexible bronchoscopy and BAL to compare the types of infection and

inflammation

? CT scanning (special X-ray scan) assessment of any lung damage by chronic

infection

The study will be completed for your child when your child has turned five

years and has had all the final tests described above.

Your rights:

? Your involvement is entirely voluntary. If you wish to withdraw from the

study at any time you will be free to do so and this will not, in any way,

affect the quality of the care you and your child receive.

? If you would like to discuss the conduct of the study with an independent

person, Dr Alison Wesley or Dr Innes Asher may be contacted via on (09) 307

4921 for an appointment or telephone conversation about the project.

? In the unlikely event of a physical injury as a result of your

participation in this study, you will be covered by the accident

compensation legislation with its limitations. If you have any queries about

ACC please feel free to ask the researcher for more information before you

agree to take part in this trial.

? If you have any queries or concerns regarding your rights as a participant

in this research, you may contact the Health Advocates Trust phone 0800 205

555

Finally:

Your participation in this study would be greatly appreciated and will help

us to determine the best strategy for managing cystic fibrosis in young

children in the future. The personal records and results collected from this

study will remain confidential and although we hope to publish the results

from this study, individuals will not be identified in any publications.

We will send you a written report of the results at the end of the study.

You will receive a study newsletter every year to tell you how the study is

going.

If you require any further information regarding this project, please

contact:

Dr Cass Byrnes, Cystic Fibrosis Consultant, (09) 3737 599 ext 6393

Jan Tate, Cystic Fibrosis Nurse Practitioner, (09) 3078 900 ext 6556

Merrin Harger, Project Manager, BAL. Study. (09) 3737 599 ext 6393

(Wednesday only)

for an appointment to discuss the project

>