Novel Interventions for the Diverse Population of Australians with Bronchiectasis

Below is the letter I was sent asking me if I wanted to participate in this study. I must say I did consider it but decided that it was against my best interests and that it really can only help the drug companies make a profit by getting the drug subsidised for the masses, and dilute the power of an otherwise useful drug.

In my opinion this type of study only helps to perpetuate the somewhat mindless attitude of Western Medicinal Research of addressing a narrow subject and totally ignoring other significant information.

To explain what I mean here I will tell you that no-where in the criteira is any consideration given to where or how the patient lives, whether or not they exercise, eat crap foods, if they work in a polluted factory, if they have cats and dogs sleeping with them etc etc. It is just a study of whether or not a drug improves their life. To me, all these people in this study should be required to that submit all of that information and then they should be divided into groups, and compared before and after the study.

Its a bit like comparing the effectiveness of fire extinguishers without knowing whether or not someone is pouring petrol on the fire !

From my own experience I have used Azythromycin 500 mg and had amazing results. It was the only drug that eliminated a prolonged infection and I always held it to be a drug I should seldom use so as to avoid any chance of my body (and the resident bugs) building a resistance to it.

This study is double blind using either saline at 7% for inhalation or the placebo of saline at 0.9% and, Azythromycin 250 mg or placebo consisting of 40mg lactose tablet. Each patient gets either / or of both so there are 4 groups. Blind Freddie can tell you that those taking the 7% saline will improve their health, it's been common knowledge amongst Brochiecatasis sufferers for a long time. I can also tell you that those getting the Azythromycin will also benefit, but both only in proportion to how much effort they make in other areas.

The downside for me is this, if I participate in the study I cannot use the saline I use every day now, and if I get the placebo my health will decline significantly, and for what, so that these Doctors can actually find out that what we have been trying to tell them for decades is actually true !!

The issue I have with handing out Azythromycin like a bag of lollies is that the bugs I will likely come in contact with in years to come will build a resistance to it and reduce the effectiveness to me.

You decide for yourself, I say NO to this kind of expensive medicine being subsidised for people who are too lazy to try to help themselves. Yes, some people really need this drug, but popping pills is NOT the answer, listening to people who have improved their lives after Doctors told them they would never improve would be a lot more useful. I have never been asked to participate in any kind of survey by these doctors to find out about my lifestyle, the foods I eat, my exercise regime, my dietary supplements etc etc. Why not start there ?

Participant Information Sheet

Introduction
You are being invited to join this research study because you have bronchiectasis. Taking part in a research study is your choice.  Important information about this research study is explained below.  Please read this information carefully and ask as many questions as you like before you to decide to join the study.

Purpose
This research study is investigating nebulised hypertonic saline and oral azithromycin for people with bronchiectasis. Hypertonic saline helps to clear the lungs by improving mucus clearance and azithromycin is an antibiotic. The objective is to investigate whether these treatments help improve quality of life, lung function, exercise capacity and reduce lung infections. Previous studies have shown that hypertonic saline and azithromycin are effective in treating people with the inherited disease Cystic Fibrosis who have bronchiectasis. This study aims to see if hypertonic saline and azithromycin are also effective in treating people with bronchiectasis due to other causes.

You are also invited to contribute two sputum samples to a sputum isolate bank for bronchiectasis at the Queensland Paediatric Infectious Diseases Laboratory, Queensland Children’s Medical Research Institute, Herston. It is hoped that research on this sputum isolate bank will help researchers to better understand the nature of bronchiectasis and assist in developing future clinical research. The study and sputum isolate bank are being conducted and overseen within this institution by: [insert names and positions of site investigators].

Study Design
In this study, we plan to invite 130 people with bronchiectasis to complete six months of treatment with twice daily nebulised hypertonic saline (or placebo) and once daily oral azithromycin (or placebo). A placebo looks exactly like the medication but does not contain any active ingredient. The treatment you receive will be decided randomly (like the toss of a coin).  Neither you nor the study doctor or staff will know whether you are taking the active drugs or placebos until after the study is completed.

The study is being sponsored by the National Health and Medical Research Council of Australia. The study will also be supported by Pari GmbH, as this company will donate eFlow rapid® nebulisers for use in this study, as well as Allen & Hanburys (Division of Glaxo Wellcome Australia Limited), who will donate ventolin metered dose inhalers and volumatic spacers for this study. Pari GmbH and Allen & Hanburys will have no other involvement in this study or its publication

Study Drug
If you qualify and join in the study, you will be given two trial medications, one will be an inhaled (nebulised) solution and the other a tablet.

1.  Trial inhalation solution will be either hypertonic saline or placebo.  The trial inhalation solution will come in a 4 mL plastic vial. The contents of the vial will be emptied into a nebuliser cup.  The trial inhalation solution will be administered as a nebulisation twice per day via an eFlow rapid ® nebuliser. The anticipated nebulisation time will be 4 minutes.  The strength of hypertonic saline in this study will be 7%.  The placebo solution will be 0.9% saline solution.

The study drug must be protected from light.  Ten ampoules will be supplied in an opaque bag and three bags are to be supplied in a box. 

2. Trial Antibiotic Tablet.  You will receive either active antibiotic therapy consisting of 250 mg of azithromycin tablets or placebo consisting of 40mg lactose tablets.  The trial antibiotic tablet will be taken once daily.

Duration
This study will last for about 7 months. During the study will you will come to the clinic for up to 5 visits.

Tests and Procedures
If you agree to participate in this study, you will be asked to sign the Participant Consent Form. You will then be asked to attend our outpatient clinic for the following:

          1) At pre-trial screening (Month -2):

• Collect demographic information such as your contact details, age, gender, height and weight. We will also record your current medications.
• Lung function test (spirometry).
• Provide a sputum sample, if you are able. If you are not able to spontaneously expectorate a sputum sample, you will be asked to undergo a sputum induction procedure. This involves breathing a sterile high salt solution via a nebuliser with encouraged deep breathing and coughing. The whole process usually lasts less than 15 minutes.
• Provide a 9mL blood sample, which will be taken from a vein in your arm, for routine testing (full blood count, electrolytes, urea, creatinine, liver function and C-reactive protein).
• Electrocardiogram (ECG) - to record your heart activity

          2) At baseline (Month 0):

• Collect demographic information such as your contact details, age, gender, height and weight. We will also record your current medications.
• Complete three quality of life questionnaires, which seek information on your lung health and breathlessness and take about ten minutes to complete.
• Lung function test (spirometry).
• Provide a sputum sample, if you are able.
• Supervised inhalation of first test dose of the trial inhalation solution (hypertonic saline or placebo). You will be asked to take two puffs of salbutamol (ventolin) first. The supervised inhalation is to make sure you tolerate the inhalation solution before you go home. Once at home, you will be asked to take this inhalation solution twice a day via nebulisation for six months.
• Perform a walking exercise test to assess your exercise capacity. We will measure your oxygen saturation and heart rate and ask you to rate your breathlessness at the start and end of the test. You will be asked to walk up and back on a 10 metre course at increasing speeds until you can no longer do so. The test takes about 10 minutes to complete.
• Provide a blood sample (approximately 9 mL or 2 teaspoons), which will be taken from a vein in your arm, for routine testing (full blood count, electrolytes, urea, creatinine, liver function and C-reactive protein).
• You will be asked to collect information in a diary documenting changes in symptoms, medications and hospital admissions

         
          3) Month 1 follow-up:

•   Complete three quality of life questionnaires.
•   Report any side effects or changes in medication.
•   Return completed weekly diary cards, documenting changes in symptoms, medications, and hospital admissions.
•   Return used ampoules of nebulisation solution and unused capsules.
•   Lung function test (spirometry).
•   Provide a blood sample, which will be taken from a vein in your arm, for routine testing.

          4) Month 3 follow-up:

•   Complete three quality of life questionnaires.
•   Report any side effects or changes in medication.
•   Return completed weekly diary cards, documenting changes in symptoms, medications, and hospital admissions.
•  Return used and unused ampoules of nebulisation solution and unused capsules.
•  Lung function test (spirometry).
•   An electrocardiogram (ECG)

          5) Month 6 follow-up:

•  Complete three quality of life questionnaires.
•  Report any side effects or changes in medication.
•  Return completed weekly diary cards, documenting changes in symptoms, medications, and hospital admissions.
•   Return used and unused ampoules of nebulisation solution and unused capsules.
•  Lung function test (spirometry).
•   Provide sputum sample If you are not able to spontaneously expectorate a sputum sample, you will be asked to undergo a sputum induction procedure. This involves breathing a sterile high salt solution via a nebuliser with encouraged deep breathing and coughing. The whole process usually lasts less than 15 minutes.
•    An electrocardiogram (ECG)
•   Perform a walking exercise test.
•   Provide a blood sample, which will be taken from a vein in your arm, for routine testing.

          6) Month 7 follow-up (one month after stopping the trial medications):

•   Complete three quality of life questionnaires.
•   Report any side effects or changes in medication.
•   Return completed weekly diary cards, documenting changes in symptoms, medications, and hospital admissions.

d)  Lung function test (spirometry).

In addition, the researchers would like to have access to your medical record to obtain information relevant to this study and sputum isolate bank.

Contributing to the sputum isolate bank
If you agree to contribute to the sputum isolate bank, you will not be required to do anything additional to the study procedures listed above. A portion of the sputum sample collected at the start (Month 0) and end (Month 6) of the trial and not required for diagnostic purposes will be placed in the sputum isolate bank. These sputum samples would otherwise be discarded. Contributing to this sputum isolate bank will have no effect on your clinical care.

In the sputum isolate bank your sputum samples and health information will be identified with a number to protect your privacy. Your name will be recorded in connection with this number, but information about you will only be linked to your number. The information will always be treated confidentially, and only Dr Scott Bell (the sputum isolate bank custodian for the study), his assistants and authorised researchers will have access to it.

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Potential Risks and Discomforts
All medical procedures - whether for diagnosis or treatment, routine or experimental - involve some risk of injury. In addition, there may be risks associated with this study that are presently unknown and unforeseeable. In spite of all precautions, you might develop medical complications from participating in this study.

There are no major risks in participating in this study. There is a slight possibility of an adverse reaction during the exercise testing, although it is extremely unlikely that any unforeseen cardiac events would occur. Your heart rate and oxygen saturation will be monitored. The test will be terminated if you request it or if the researchers decide this is necessary for your well-being.

Blood collection involves some discomfort at the site from which the blood is taken. There is also a risk of some minor bruising at the site, which may last one to two days.

Minor risks from the nebulised trial solution include: the inhalation of the hypertonic saline may cause you to experience some chest tightness, wheezing and even a drop in your oxygen saturation or temporary drop in your lung function. To minimise this, we will give you a bronchodilator medication (ventolin) that opens up the airway prior to the inhalation and we may ask you to withdraw from the study if you cannot tolerate the inhalation. You will be supervised and given a test dose of the nebulised trial solution at the baseline visit to monitor for any side effects before you are started on it regularly at home. As well, we ask that you report any side effects you are experiencing to us and your respiratory doctor.

There is a very small amount of quinine sulphate in the trial inhalation solution. Quinine sulphate acts as a taste-masking agent, to disguise the salt taste of the solution. The amount of quinine in the solution is much less than that contained in a small bottle of tonic water. There are only very rare and specific medical circumstances where this could be a problem and if they are relevant to you, we would not include you in the trial.

There are unlikely to be many potential risks from the azithromycin capsules, as side effects in all trials of azithromycin have been uncommon and limited to predictable antibiotic reactions and increases in bacterial antibiotic resistance have been clinically insignificant. If you have a known allergy to macrolide antibiotics or are currently prescribed any medication that is contraindicated by macrolide antibiotics, we would not include you in the trial.

Medications that should not be taken during the trial
There are some medications, both over-the-counter and prescribed, that you should not take during the trial. Tell the doctor/researcher if you are taking any of these medications:

• Medications used in migraine and cluster headaches such as ergotamine (e.g. Cafergot), methysergide (e.g. Deseril) and dihydroergotamine (e.g. Dihydergot);
• Medications used for heart arrhythmia (e.g. irregular heart beat) such as dronedarone (e.g. Multaq), disopyramide (e.g. Rythmodan), amiodarone (e.g. Aratac), sotalol (e.g. Sotocor) and digoxin (e.g. Lanoxin);
• Warfarin (e.g. Coumadin);
• Medications that control mood swings such as pimozide (e.g. Orap), ziprasidone (e.g. Zeldox), hexobarbital (e.g. Evipan), amisulpride (e.g. Solian), haloperidol (e.g. Serenace), droperidol (e.g. Droleptan) and sertindole (e.g. Serdolect);
• Some antidepressants such as amitriptyline (e.g. Endep), clomipramine (e.g. Anafranil), dothiepin (e.g. Dothep), doxepin (e.g. Deptran), imipramine (e.g. Tofranil), nortriptyline (e.g. Allegron) and trimipramine (e.g. Surmontil);
• Immunosuppressants such as cyclosporine (e.g. Neoral) and tacrolimus (e.g. Prograf);
• Medications used to control seizures such as phenytoin (e.g. Dilantin) and carbamazepine (e.g. Tegretol);
• Cabergoline (e.g. Cobasol, Cabaser);
• Colchicine (e.g. Colgout);
• Anti-infectives such as atazanavir (e.g. Reyataz), clarithromycin (e.g. Klacid), erythromycin (e.g. Eryc), fluconazole (e.g. Diflucan), mefloquine (e.g. Lariam), moxifloxacin (e.g. Avelox), pentamidine (e.g. Pentam), quinine (e.g. Quinbisul), voriconazole (e.g. Vfend), zidovudine (e.g. Retrovir), nelfinavir (e.g. Viracept) and rifabutin (e.g. Mycobutin);
• Medications used in the treatment of some cancers such as dasatinib (e.g. Sprycel), lapatinib (e.g. Tykerb), nilotinib (e.g. Tasigna), sunitinib (e.g. Sutent), pazopanib (e.g. Votrient) and arsenic trioxide (e.g. Phenasen);
• Theophylline (e.g. Nuelin);
• Vardenafil (e.g. Levitra);
• Cisapride (e.g. Propulsid);
• Illicit drugs, such as cocaine, can also interact with azithromycin.

Medications that should only be taken with caution during the trial
There are some medications, both over-the-counter and prescribed, that should only be taken with caution during the trial. Tell the doctor/researcher if you are taking any of these medications:

• Antacids that contain aluminium or magnesium (e.g. Mylanta, Gaviscon). The trial tablet (e.g. azithromycin or placebo) must be taken at least one hour before the antacid or at least two hours after the antacid.
• Triazolam (e.g. Halcion);
• Reboxetine mesylate (e.g. Edronax);
• Medications used in pain management such as fentanyl (e.g. Durogesic), oxycodone (e.g. Endone) and methadone (e.g. Physeptone);
• Medications used to lower cholesterol such as lovastatin (e.g. Altoprev), simvastatin (e.g. Zocor) and atorvastatin (e.g. Lipitor). Caution patient and monitor for muscle pain.

It is important that women participating in this study are not pregnant and do not become pregnant during the course of the study. If you are a woman of child-bearing potential and there is any possibility that you are pregnant, the researchers will perform a pregnancy (urine) test before you start in the study. If necessary, you should use reliable contraception (such as oral or implanted contraception, an IUD or have had a tubal ligation) during the course of the study. If at any time you think you may have become pregnant, it is important to let the researchers know immediately.

Potential Benefits
While we intend that this research study and sputum isolate bank further medical knowledge and may improve treatment of bronchiectasis in the future, they may not be of direct benefit to you.

Alternative Treatment
You do not have to participate in this study to receive treatment for your bronchiectasis.  Your doctor will discuss any other treatment options available to you.

New Findings
You will be given any new information gained in a timely manner during the course of the study that might affect your willingness to continue your participation. 

Study Records
Your study records will be kept confidential.  However, your patient chart may be reviewed by the Institutional Ethics Committee overseeing this trial, the United States Food or other regulatory authorities to ensure that the study is being correctly performed.  In any of these cases, your identity will be kept confidential.  Additionally, your name will not be disclosed in any publications or presentations. By signing a written informed consent form you or your legally acceptable representative is authorizing access to your medical records.

In Case of Injury
If you suffer any injuries or complications as a result of this study, you should contact the study doctor as soon as possible, who will assist you in arranging appropriate medical treatment. If you are eligible for Medicare, you can receive any medical treatment required to treat the injury or complication, free of charge, as a public patient in any Australian public hospital.

In addition, you may have a right to take legal action to obtain compensation for any injuries or complications resulting from the study. Compensation may be available if your injury or complication is sufficiently serious and is caused by unsafe drugs or equipment, or by the negligence of one of the parties involved in the study (for example, the researcher, the hospital, or the treating doctor). You do not give up any legal rights to compensation by participating in this study.

Cost to Participants
Participation in this study and sputum isolate bank will not cost you anything, nor will you be paid. However, if funds permit, you will be reimbursed for your travel expenses for study visits. As well, each participant will receive his/her own Pari eFlow rapid® nebuliser at the end of the study.

Right to Refuse or to Withdraw from the Study
Participation in this study and contribution to the sputum isolate bank are entirely voluntary. You do not have to take part in them. If you do take part, you can withdraw at any time without having to give a reason. You can also withdraw your sputum samples and health information from the sputum isolate bank at any time without having to give a reason. Whatever your decision, please be assured that it will not affect your medical treatment or your relationship with the staff who are caring for you. Of the people treating you, only those named above will be aware of your participation or non-participation.

Sometimes during the course of a study, new information becomes available about the treatment that is being studied. While you are participating in this study, you will be kept informed of any significant new findings which may affect your willingness to continue in the study.

Confidentiality
All the information collected from you for the study and sputum isolate bank will be treated confidentially, and only the researchers named above will have access to it. The study results and results of research conducted using the sputum isolate bank may be presented at a conference or in a scientific publication, but individual participants will not be identifiable in such a presentation.

Results of the Study
These are published in medical journals that are available to the public. You should feel free to ask the study staff about this. A plain English summary of the study results will be made available to you through the study doctor if you wish.
Who to Contact:
When you have read this information, [name of researcher] will discuss it with you further and answer any questions you may have. If you would like to know more at any stage, please feel free to contact [him/her] on [telephone number].

Institutional Review Board/Research Ethics Board:
This research will be conducted in accordance with the National Statement on Ethical Conduct in Research Involving Humans, the Helsinki Declaration and subsequent amendments and NHMRC guidelines.

The Research Ethics Committee of The Prince Charles Hospital Metro North Health Services District has approved this study.  Should you wish to discuss this study with someone not directly involved, in particular matters concerning policies, information about the conduct of the study or your rights as a participant, or you wish to make a confidential complaint at any time, you may contact:. 

The Prince Charles Hospital Research and Ethics
Rode Road
            Chermside. Qld 4032
Phone: 07 3139 4500

Revocation of Consent Form - Participant

• I hereby wish to WITHDRAW my consent to participate in the research project described above and understand that such withdrawal WILL NOT jeopardise any treatment or my relationship with (insert name of institution here).

Participant’s name (please print):  .........................................................................................

(Signature)..............................................................                         Date:_ _ / _ _ _ / _ _ _ _
                                                                                                               DD / MMM / YYYY

                       
This Revocation of Consent should be forwarded to:

(sites to insert institution investigator details)