HYDROCORTISONE FOR PREVENTINGBRONCHOPULMONARY DYSPLASIA; THE STOP-BPD STUDY

PARENT INFORMATIONLETTER

Dear Sir, Madam,

Your baby has been admitted to the Neonatology Department because it was born prematurely. All members of the medical team are currently doing their utmost to help your child get through this difficult period in the best way possible. Your physician will undoubtedly have told you that most treatment procedures we have at our disposal may not be without adverse effects. Fortunately, we know that the benefits of many therapies far surpass theirdisadvantages.There arealsotypes of treatment, however, as yet unproven, which are presumedto be more beneficial than detrimental.Proof for such a presumption can only be obtained by conducting research, which will enable us to continually improve the level of care we can offer premature babies.

The purpose of this letter is to inform you about an important clinical research study that is currently being carried out at all neonatology departments in the Netherlands.

Background and object of the study

Your babyis still incapable of absorbing sufficient amounts of oxygen into its bloodstream through independent breathing and has therefore been put on a respirator. Yet such artificial respiration may cause damage to the baby’s immature lungs. If the damage becomes extensive, a condition arises that we refer to as bronchopulmonary displasia, abbreviated to BPD.

Babies with BPD require more time before they are able to breathe entirely on their own and often need extra oxygen for a considerable period. During the first few years of their lives, they may frequently suffer from pneumonia and shortness of breath, for which they will have to take medicines. And if we look even further ahead, it becomes apparent that children with BPD tend to lag behind in both physical and mental development in comparison with other prematurely born children without BPD. So you will understand that we, as medical practitioners, will do everything in our power to prevent BPD.

Administering adrenal gland hormone is one of the available methods of treatment. Two types of adrenal gland hormone are currently used in the Netherlands: dexamethasone and hydrocortisone. Research has brought to light that dexamethasone does reduce the incidence of BPD, but this therapy may have significant side-effects, such as high blood sugar levels, hypertension, gastro-intestinal problems, infections and, possibly, enhanced probability of lagging behind in physical and mental development. There are strong indications that hydrocortisone has fewer adverse effects, but we still lack conclusive proof that this treatment actually decreases the risk of BPD.

That is why all 10 neonatology departments in the Netherlands have decided to look further into hydrocortisone therapy for the prevention of BPD in premature babies. In total, over 400 children will participate in the study.

What children qualify for participation in the study?

Babies who are at risk of developing BPD. This includes children born after a pregnancy of 24 to 30 weeks and/or with birth weights lower than 1250 grams, who need supplemental oxygen in the 2nd week of life.

What precisely does this study involve?

Babies participating in this study will receive either hydrocortisone therapy for 22 days or will be given a so-called placebo (a substance without any medical effect) from their second week of life. Which of the two types of treatment you baby will receive is unknown in advance; it will be decided by drawing lots. The study will be conducted ‘double blind’, which means that neither doctors, nurses nor parents will know which therapy is being administered to your baby. Nothing will change in the further care or treatment of your baby. Nor will your child be subjected to any additional examinations, although we will, of course, continue to monitor your babyclosely, recording lots of data during its stay at the hospital.

When your baby is 36 weeks old, counting from the mother’s last period (4 weeks prior to the calculated date of birth), we will determine whether your child has a form of BPD.

As usual, your baby will have to be checked on a regular basis at the outpatient clinic of the neonatology department. A development test will be performed 24 months after the calculated date of birth. This data, too, will be incorporated into the study file.

How will the study impact your child and what are the pros and cons?

The medicine will be administered intravenously. Considering that most prematurely born babies are on a drip anyway, administration will cause no extra impact on your child. Should your baby no longer require a drip, hydrocortisone or placebo can also be given with food. As mentioned previously, your child will continue to receive standard care and treatment, and no additional examinations are required for this study.

A possible advantage of hydrocortisone therapy could be that your baby has a diminished risk of developing BPD and thus a greater chance of avoiding all future problems associated with the condition. A possible disadvantage of hydrocortisone therapy could be that your baby might be exposed to an increased risk of side-effects brought on by adrenal gland hormone use, such ashigh blood sugar levels, hypertension, gastro-intestinal problems, infections and, possibly, enhanced probability of lagging behind in physical and mental development.

It goes without saying that your child’s health is of paramount importance, which is why your baby is closely monitored all the time. Your attending physician can decide at any time to discontinue your baby’s participation in the study, if he/she thinks that a different type of treatment is required, which falls outside the scope of this study. You will, of course, be notified if such should be the case.

What do we request your permission for?

We ask your permission for your baby’s inclusion in this research study.Participation in the study is entirely voluntary, which means that you can withdraw your child from the study at all times, without any consequences for the treatment and care your child will receive. If your child participates and should be transferred during the study to a hospital in your area, your consent will also involve allowing us to retrieve data on the course of your child’s condition during this part of the research study.

In addition, we would like to ask your permission to approach you at a later date, after the study has been completed, for additional research.

Confidentiality of data

For reasons of privacy protection, all research and medical data will be recorded under code, i.e. anonymously, and thus kept fully confidential. Your baby’s name will neither be used nor made visible. The identity of study subjects can only be retrieved by the researchers and attending physicians. It may be necessary, however, that certain parties be allowed to inspect medical files for trial monitoring purposes, such as representatives from the AMC’s Medical Ethics Committee orfrom the study’s initiator, the AMC, or duly authorised government bodies. Access to the files is then granted under the responsibility of the attending physician. If you consent to your child’s participation in this study, you automatically agree to such inspections. Your child’s identity will never be disclosed for any other reason. The data recorded within the scope of this study will be kept by us for 20 years and then be destroyed. The AMC’s Medical Ethics Committee has given this clinical trial a favourable opinion.

Insurance

In pursuance of Section 7 of the Dutch Medical Research Involving Human Subjects Act (published in the 1998 Bulletin of Acts and Decrees, p. 161), insurance has been taken out for the subjects participating in this study (see appendix). This insurance complies with the stipulations set forth in the Decree on Compulsory Insurance of Medical Research Involving Human Subjects (published in the 2003 Bulletin of Acts and Decrees, p. 266).

Further information

Should you have any further questions in regard to this study, you can contact one of the responsible researchers at telephone number ...... :

If you have any questions that you would rather not discuss directly with the researcher, you can turn to an independent physician who is not involved in the conduct of this study. In this case, the physician in question is ...... , who can be reached at telephone number ......

On behalf of the national and local research team,

………………………………………………………..

Appendix: Information on AMCAmsterdam Insurance

Pursuant to the Dutch Act on Medical Research involving Human Subjects, the private limited liability company AMC Medical Research B.V. has taken out insurance covering any and all fatal and non-fatal injuries suffered by subjects due to participation in clinical studies organised by the same.

  1. Any such injury as referred to above should become apparent and be reported during the subject’s participation in a particular study or within four years thereafter.
  2. The sums insured amount to € 450,000 per subject, to a maximum of €3,500,000 for the entire study and a total of € 5,000,000 per insurance year for all reported injuries caused by any medical research trials involving the company mentioned above.

The insurance provides cover:

  1. for any injury sustained as a result of the realisation of any risk connected with participation in a clinical study, of which the subject had not been notified in writing beforehand;
  2. for any injury sustained as a result of the realisation of any risk in respect of which the subject had in fact been notified, but the ramifications of which turned out to be more serious than anticipated;
  3. for any injury sustained as a result of the realisation of any risk in respect of which the subject had in fact been notified, but the occurrence of which was considered extremely unlikely.

The insurance does not provide cover:

  1. for any injury resulting from the non-occurrence of any amelioration of a subject’s health problems or from the further deterioration of the subject’s health, in the event that treatment of the subject’s health problems is the reason for his or her participation in a particular trial;
  2. for any injury resulting from any impairment of a subject’s health, which would most likely also have occurred if the subject had not participated in the trial;
  3. for any injury resulting from participation in a clinical trial involving comparisons of medical acts customarily performed by medical professionals, where it is probable that the damage has been caused by any such act;
  4. for any injury revealing itself in a subject’s offspring and resulting from adverse effects of the study on either the subject or the offspring of the same;
  5. for any injury resulting from the subject’s complete or partial failure to follow directions and instructions, provided that the subject is capable of doing so.

The insurance exclusively covers injuries sustained by natural persons.
Cover of specific injuries and expenses is limited to specified sums.

In order to qualify for compensation under the insurance, the subject is to lodge any and all personal injury claims related to the study with:
Name of insurer: Centramed B.A.
Address of insurer: Prinses Beatrixlaan 35, 2595 AK The Hague,The Netherlands.
Policy number: 620.872.806

In regard to such matters, the subject is furthermore requested to contact:

Dr A.H. van Kaam: +31 (0)20-5663477 and Ms M.A. Mooijer +31 (0)20-5666264

Parent Information Letter SToP-BPD Study. Version 2 05-01-2011. Academic Medical Centre Amsterdam.

1