Full Project Title:

Safety and preliminary efficacy study for the Accessa™ system for the treatment of patients diagnosed with Over Active Bladder (OAB)

 

Principal Researcher: Dr Bruce Farnsworth             

1. Your Consent

You are invited to take part in this research project.

This Participant Information contains detailed information about the research project. Its purpose is to explain to you as openly and clearly as possible all the procedures involved in this project before you decide whether or not to take part in it.

Please read this Participant Information carefully. Feel free to ask questions about any information in the document.  You may also wish to discuss the project with a relative or friend or your local health worker. Feel free to do so.

Once you understand what the project is about and if you agree to take part in it, you will be asked to sign the Consent Form. By signing the Consent Form, you indicate that you understand the information and that you give your consent to participate in the research project.

You will be given a copy of the Participant Information and Consent Form to keep as a record.

2. Purposes and Background

The purpose of this project is to determine whether Accessa™-I, a new medical device, is safe and effective to use for the treatment of female OAB.  OverActive Bladder (OAB) is a syndrome encompassing urgency, increased daytime frequency, nocturia and sometimes urge incontinence. Urgency is the complaint of a sudden compelling desire to pass urine that is difficult to defer; increased daytime frequency is the complaint of voiding too often by day and nocturia is by night. Urge incontinence is characterized by a strong desire to void coupled with an involuntary loss of urine. These terms are used in the absence of no urinary tract infection or other obvious pathologies. Furthermore, the syndrome may or may not be related to urodynamically demonstrable detrusor overactivity, which is characterized as involuntary detrusor contractions during filling phase that are either spontaneous or provoked.

OAB can have a profound effect on patients’ quality of life (QOL) producing social, psychological, occupational, domestic, physical and sexual problems. This distressing condition can influence anyone at any age. Worldwide, OAB syndrome is estimated to affect no less than 50 million people in the developed world.

People with OAB symptoms do not seek help for their condition for many reasons including embarrassment and lack of awareness of the abnormality of symptoms at any age and can be managed effectively .

 

Although there are many treatment options for patients with OAB syndrome, all have limitations and some are associated with significant side effect that may reduce acceptance by OAB patients.

 

 

AMS Accessa™-system is an experimental, electrical stimulator system which is not registered or approved for use for treatment for Over active bladder in Australia. The system consists of an electrostimulator and a stimulation lead which are both implanted under the skin. The stimulator delivers mild electrical pulses via the stimulation leads to the pelvic floor muscles.

 The study will last for a period of about 1 year. However, once the study is over, you will continue to be looked after by your doctor for a period of up to 5 years after the surgery.

The safety of the system will be determined by counting the number of problems that occur during the study, such as pain or discomfort, or more serious problems that might need admission to hospital.

The efficacy of the system will be determined according to patients’s respond to the Accessa™ treatment; favourable response will be demonstrated by sustained improvement in urinary frequency, degree of urgency, leaking episodes, and their quality of life at the follow up visits.

So far, eleven patients, (average age 59 years) have been recruited to previous studies to evaluate the implant system in South Africa and England. All patients suffered severe OAB symptoms for several years which have continued despite all standard other treatments. So far 4 patients did not continue with the procedure/ treatment because the device did not give them improvement. Four women were completely dry at the last visit and eight out of ten (80%) reported significant improvement after implant of the Accessa™ therapy,  in various aspects of quality of life based on patient’s questionnaires. Moreover, following the treatment urge incontinence completely ceased in four patients, while the number of leaking episodes decreased significantly in the rest. In addition the patient’s urinary frequency reduced by 38%.

 

Four patients experienced procedure-related adverse events due to lead migration, wound infection, system withdrawal and re-suturing.

 

A total of 30 patients will be recruited to this study.

 

You are invited to participate in the study, because your physician believes that the condition from which you suffer may benefit from application of the device under investigation.

This study is being conducted internationally by the manufacturer of the device:

 

American Medical Systems

Minnesota, USA

 

Who specialises in developing and marketing of advanced implantable devices. They will pay your medical expenses to the centre to include you in the study.

3.         Procedures

AMS Accessa™-I system is an experimental, electrical stimulator system. The Accessa™-I system consists of an electrostimulator and a stimulation lead which are both implanted under the skin. The stimulator delivers mild electrical pulses via the stimulation lead to the pelvic floor muscles.

The Accessa™-I is about the size of a cigarette lighter and its dimensions are 47X53X10 mm. The stimulation lead (a thin wire) is 35 cm long and its diameter is 1.4mm.

The best stimulation levels will be determined according to your sensations. The electric pulse induces relaxing effects on the bladder wall to allow you to permit bladder filling to be more comfortable and on the other hand induce muscle contraction to help you avoid urine leakage.

A communication system, which is connected to a laptop computer, allows your doctor to control the implanted system after it is implanted.

 

System components are illustrated in figure 1.

 

 

 

 

                                      Figure 1: Accessa™-I system

You will receive a patient identification card with details about your implanted system and emergency contact persons in Australia. You should carry your system ID card with you all the time.

 

General
If you decide to take part in the study you will be recruited to the study for 12 months (1 year). The research itself will last for several more years until all patients are recruited and have completed the study.

 

The Accessa ™-I therapy involves two stages:

a. Accessa™-I test system (MTS-I)

b. Surgical implantation of the system.

Patients who get relief from their OAB symptoms with the test system would then be offered the long-term implant.

 

Recruitment visit

Before you try the test system your doctor will go through your medical history with you. You will need to have a urodynamics test. This testing involves taking pressure measurements form the bladder and urethra (the tube from which you urinate) using a small catheter and from the vagina or rectum using a second small catheter while your bladder is filled with sterile water. The test is routinely performed on women with bladder control problems. You will be given one dose of an antibiotic before the urodynamics testing in order to minimise the chance of getting a urinary tract infection. Your doctor will also collect a blood and urine sample to test for urinary tract infection and blood will be taken (about 2 to3 teaspoons or 10-15ml) from an arm vein. These samples will be processed in the hospital laboratory and samples will be destroyed as per routine tests. These are routine examinations done to patients diagnosed with OAB.

Additionally, your doctor needs to know:

·       How long you’ve had OAB

·       If you have any other urinary symptoms

·       What past procedures or prescription drugs you have tried

·       If you have any other diseases or illnesses

·       What medications you are currently using

You will be asked to fill-in questionnaires and a voiding diary at home for a period of 3 days before your visit to the hospital. In the voiding diary you will be asked to write down your symptoms (voiding habits) for 3 consecutive days. This will give your doctor a “baseline” record of your symptoms prior to the therapy. This information will help you and the doctor to decide whether you are suitable to the Accessa™-I test system.

 

Accessa™-I Test System visit

Accessa™-I Test System (MTS-I) is the first step of Accessa ™-I therapy. The MTS-I consists of electrical stimulating device, about the size of a cigarette lighter that is worn on a pouch belt around your waist. The electrostimulator delivers mild intermittent electrical pulses to the pelvic muscles. The lead would be placed in a very small cut near the vagina. This procedure will be performed under local anaesthetic to minimise discomfort. After placement of this trial system it is necessary to be monitored in hospital for 48 hours

After being connected to the test system your doctor will set the best stimulation level, using a communication system, according to your sensations (comfortable, but aware of the stimulation).  Once individual settings have been programmed, you will receive an explanation about how to use the temporary device.

 

You will be asked to wear the system for at least 48 hours and record in the voiding diary how the therapy affects your symptoms. Your symptoms may improve or even completely disappear. Whenever an event of discomfort is felt, you are asked to turn the system OFF using the safety magnet that will be given to you, and immediately contact your doctor.

During the MTS-I test you will be asked not to alter your daily fluid intake and to record your bladder symptoms in the voiding diary. You will be asked not to take a bath or a shower in order to avoid getting the system wet or pulling the lead out by accident. You will be asked to avoid sexual intercourse during the test period to prevent lead displacement.

 

The test procedure has several advantages.

·       It’s a temporary procedure in which you can learn whether the Accessa™-I therapy can help you without committing to a long-term treatment.

·       It allows you to “test drive” the Accessa™-I therapy.

·       It allows you to feel what stimulation is like. 

 

At the end of the 48 hour test, the system is removed by your doctor while you are still in hospital. Based on the results of your test trial, your doctor may recommend an implantable Accessa™-I system to improve your bladder symptoms.

 

Accessa™-I implantation

The implantation of the Accessa™-I system is the beginning of the second stage of the study. The electrostimulator and stimulation lead are both implanted under the skin under local or general anaesthetic (depending upon your choice after discussion with the Anaesthetist). Doctors usually implant the Accessa ™-I system in two steps: First, the stimulation lead and then the electrostimulator. This entire procedure typically takes 25 to 40 minutes and is performed in the operating theatre. You will be prescribed antibiotic medication in order to reduce the risk of infection after the surgery and can go home the same day if you feel comfortable.

 

In order to implant the system, the doctor will make two small cuts:

One 4 cm cut in your lower abdomen just above the pubic bone, where the electrostimulator is positioned; the second a tiny cut, where the stimulation lead tip is inserted near the vaginal opening.

 

System activation visit

Two weeks after the procedure, you will return to your clinic, where the doctor will remove your sutures and will set the stimulation levels for you, using a communication system connected to a laptop computer. The stimulation level will be set according to your sensations (comfortable, but aware of the stimulation).

This visit will take approximately one hour and will be performed in the outpatient clinic.

You will receive a safety magnet that allows you to control the internal device by switching it ON or OFF (identical to the one used during MTS-I procedure) if you feel it is necessary.

 

 

Follow up visits

You will be asked to attend follow-up visits 1, 3, 6 and 12 months after the activation of the implanted system. Each visit will last approximately 20 minutes at you doctor’s clinic. Between the visits we will ask you to complete the voiding diary for 3 consecutive days to record how the treatment affects your voiding symptoms.

The change in symptoms will be estimated according to your personal impressions. Your symptoms may remain the same, worsen, improve, completely disappear or may not alter. It is unexpected though possible that the sensations would be worse. During these visits, you will be asked to fill in a quality of life questionnaire. Additionally, you may discuss your urinary symptoms with your doctor and decide whether the stimulation levels need adjustment. If so, your doctor will be able to make the necessary changes.

 

Once the study is over you will continue to be followed up by your doctor every six months for a period of 5 years.

Other than the above visits, you are not expected to need to visit the GP more often than for your usual treatment. We will pay all study-related travel expenses. 

 

4. What do I have to do?

 

Lifestyle limitation

As with any surgery you should let your body heal. Right after the surgery you should “take it easy “and avoid lifting heavy things, stretching and avoid causing strain on the abdominal stitches. You will be asked to avoid sexual intercourse and bathes (showers are allowed) for the first 2 weeks.

 

Medical procedures

You should always tell other doctors and nurses that you have an implanted electrostimulator device. The right safety measures will allow most medical procedures to be performed. Some investigations, such as Magnetic Resonance Imaging (MRI – a type of medical imaging), and some treatments, are not possible. We will advise you at the first visit regarding any special precautions you may need to take in the future.

 

Home or occupational environment

You will be given a safety magnet in order to switch the device off immediately if you feel it is necessary. The safety magnet may damage televisions, computer disks, credit cards, and other items affected by strong magnetic fields. You should always store your magnet with its protective plate.

It is recommended that while using the implanted system you should not operate potentially dangerous equipment such as power tools.

Home appliances that are properly grounded should not interfere with the Accessa™-I system operation, and may be used while the device is switched on.

 

Theft detectors and screening devices

Theft detectors found in department stores and airport/security-screening devices may cause the electrostimulator output to switch ON or OFF. It is also possible that you will experience a momentary increase in your perceived stimulation as you pass through these screening devices. Higher levels can be unpleasant or “shocking”. If you experience a change in stimulation levels you should exit from the screening device. Those devices do not damage the system, and it will continue to work normally afterwards.

Your doctor will provide you with a card showing that you are implanted with an electrostimulator to show to airport and store security if necessary. 

 

Other than the above mentioned the Accessa™-I will not cause any lifestyle limitation and you can continue your regular day routine.

5.    Possible Benefits

The Accessa™-I treatment can potentially reduce the need for analgesics (pain killers), improve urinary symptoms and increase your overall health and quality of life. Moreover, the Accessa™-I treatment is completely reversible and can be turned off at any time. The Accessa™-I system can be completely removed from your body at any time, at your request.

Results from past studies show that the Accessa™-I treatment is an effective treatment for most IC patients treated so far.

Positive impact of the Accessa™-I therapy has been demonstrated in various aspects of quality of life.

We hope that the treatment will help you, although this cannot be guaranteed. The information we get from this study is likely to improve our understanding of OAB and to provide effective relief of symptoms for people who are suffering the effects of OAB.

6.  Possible Risks

Possible risks, side effects and discomforts related to this study are the side effects of surgery (infection, skin irritation, blood clotting, pain, etc.), anaesthesia (allergy or sensitivity to anaesthetic drug, breathing arrest, etc.), and electrical stimulation (transient electric shock, painful or irregular stimulations, tissue damage, etc.).

In any case, whenever you feel an unusual or unexpected event or you experience less control of your symptoms or you become concerned, you should contact your doctor (detailed below and in your system ID card).

 

The possible risks include, but are not limited to, bleeding during the insertion operation; pain where the electrostimulator unit is implanted in the abdomen; movement of the lead leading to technical problems; pain where the lead is sited; infection; sensation of momentary electrical “shock”; skin irritation; expulsion of the device from your body; failure of the system to function properly; unsatisfactory changes in bladder and bowel functions; allergic reaction; and other technical problems.

 

 

 

 If you own a private medical insurance plan you should consult with the insurance company before agreeing to take part in the trial.  You will need to do this to ensure that your participation will not affect your medical insurance.

 

Sometimes, during a clinical trial, patients may be diagnosed with a medical condition that they are not aware of. Guidelines exist to assist in the fair determination of whether the device caused a given medical condition if it occurs coincidently during the period of treatment with the Accessa™-I therapy.

If it were determined that the new medical condition is not related to the Accessa™-I therapy you will be treated for this new condition by your doctor. If the new medical treatment will affect the Accessa™-I treatment your doctor might recommend that you withdraw from the study and the Accessa™-I will be removed from your body.

 

The effects of treatment on the unborn child and on the newborn baby are not known.  Because of this, it is important that study participants are not pregnant or breast-feeding and do not become pregnant during the course of the study.  You must not participate in the study if you are pregnant or trying to become pregnant, or breast-feeding.   If child bearing is a possibility, you will be required to undergo a pregnancy test prior to commencing the study. Participants are strongly advised to use effective contraception during the course of the study.  You should discuss methods of effective contraception with your doctor.  If you do become pregnant whilst participating in the study you should advise your treating doctor immediately.  He/she will withdraw you from the study and advise on further medical attention should this be necessary.  You must not continue in the study if you become pregnant.  There may be additional unforeseen or unknown risks.

7.  Other Treatments Whilst on Study

It is important to tell your doctor and the research staff about any treatments or medications you may be taking, including non-prescription medications, vitamins or herbal remedies and any changes to these during your participation in the study. 

8.   Alternatives to Participation

You do not have to participate in this research project to receive any medical care you may require The first line of therapeutic alternatives for the management of OAB is lifestyle adaptation use of pads and other types of sanitary protection . Additional treatment approaches can as well include the following:

1.      Behavioral therapy: bladder training, managing fluid and diet, timed and prophylactic voiding. Only half of the patients gain relief from those therapies.

2.      Pharmacologic management: antimuscarinic drugs, tricyclic antidepressants, calcium channel blockers, potassium channel openers and prostaglandin inhibitors. While the variety of pharmacological agents available for the treatment of OAB patients, their efficacy might be limited by a wide range of side effects including dry mouth and blurred vision, as well as gastrointestinal, cardiovascular and central nervous system effects, that make them particularly undesirable for use in the elderly.

3.      Intravesical drug delivery: alternative to oral medication often used to treat patient with severe detrusor overactivity..

4.      Surgical interventions: endoscopic hydrostatic distension of the bladder, enterocystoplasty, and detrusor myectomy. This line of method does not provide longterm symptom relief in most patients and usually is employed only with the significant complications.

5.      Neuromodulation: electric stimulation, transcutaneous electric nerve stimulation and magnetic stimulation. Neuromodulation is a new approach being increasingly used for the management of OAB symptoms. Effectiveness results of those techniques are limited and may provide relief to subsets of patients with OAB .

 

 

 

9.       Privacy, Confidentiality and Disclosure of Information.

 In accordance with relevant Australian and/or Victorian privacy and other relevant laws you have the right to access the information collected and stored by the researchers about you. You will have the right to request access to information from Dr Farnsworth the principal researcher if you would like to access your information. The data collected will be coded and identified with your initials, date of birth and kept in a locked office. Stored for 15 years and destroyed by shredding after that time.

Any information obtained in connection with this research project that can identify you will remain confidential and will only be used for the purpose of this research project. It will only be disclosed with your permission, except as required by law.

Your health records and any information obtained during the study may be subject to inspection (for the purpose of verifying the procedures and the data) by the Food and Drug Administration (FDA) of the United States of America (USA), other national drug regulatory authorities such as the Australian Government’s Therapeutic Goods Administration (TGA) and authorised representatives of the Sponsor, American Medical Systems Pty Ltd or as required by law. By signing the attached Consent Form, you authorise release of, or access to, this confidential information to the relevant study personnel and regulatory authorities as noted above.

In any publication, information will be provided in such a way that you cannot be identified

 

It is desirable that your family doctor be advised of your decision to participate in this research project. By signing the Consent Form, you agree to your family doctor being notified of your decision to participate in this research project.

10.  New Information Arising During the Project

During the research project, new information about the risks and benefits of the project may become known to the researchers. If this occurs, you will be told about this new information. This new information may mean that you can no longer participate in this research. If this occurs, the person(s) supervising the research will stop your participation. In all cases, you will be offered all available care to suit your needs and medical condition.

11.  Results of Project

Results of the research will be published during the study and after it has finished. You will be able to receive copies of the publications from your research doctor upon request and from scientific medical literature. Your identity will remain strictly confidential in such scientific publications.

12.  Further Information or Any Problems

If you require further information or if you have any problems relating to this project (for example, any side effects), you can contact the principal researcher. The researcher responsible for this project is Dr Bruce Farnsworth (02 94738555).

 

14.  Participation is Voluntary

Participation in any research project is voluntary. If you do not wish to take part you are not obliged to. If you decide to take part and later change your mind, you are free to withdraw from the project at any stage.

Your decision whether to take part or not to take part, or to take part and then withdraw, will not affect your routine treatment, your relationship with those treating you or your relationship with the Sydney Adventist Hospital.

Before you make your decision, a member of the research team will be available so that you can ask any questions you have about the research project. You can ask for any information you want. Sign the Consent Form only after you have had a chance to ask your questions and have received satisfactory answers.

If you decide to withdraw from this project, please notify a member of the research team before you withdraw. This notice will allow that person or the research supervisor to inform you if there are any health risks or special requirements linked to withdrawing.

15.  Reimbursement for your costs

You will not be paid for your participation in this study except that the sponsor would reimburse all travel expenses incurred as a result of your participation in the study.

16.  Ethical Guidelines

This project will be carried out according to the National Statement on Ethical Conduct in Research Involving Humans (June 1999) produced by the National Health and Medical Research Council of Australia. This statement has been developed to protect the interests of people who agree to participate in human research studies.

The ethical aspects of this research project have been approved by the Human Research Ethics Committee of Sydney Adventist Hospital.

17.  Injury

In the event that you suffer an injury as a result of participating in this research project, hospital care and treatment will be provided by the public health service at no extra cost to you.

18.  Termination of the Study

This research project may be stopped for a variety of reasons. These may include reasons such as: unacceptable side effects, the device being shown not to be effective, the device being shown to work effectively and not require any further study, investigation and decisions made in the commercial interests of the sponsor. The Accessa™-I treatment is not available in Australia yet. The sponsoring company has an approval to market the product in Europe.
If the treatment is not available on the market by the time your electro stimulator’s battery runs out, or the sponsor decided to end the study, your doctor will recommend other available treatments for your medical condition.

 

You should know that after one year of follow up, at the end of the study, the implanted system will not be removed. The system is expected to work for a period of approximately 5 years. During this time you will be followed-up by your doctor every 6 months. If side effects occur or you no longer wish to take part in the study or have the device replaced it will be removed by Dr Farnsworth. After the 5 year period (as the batteries will need replacement) a new replacement stimulator will be inserted.