03/08/2011 IRB# 1002-015

CHILDREN'S HOSPITALS AND CLINICS of MINNESOTA

2525 Chicago Avenue South 345 North Smith Avenue

Minneapolis, MN 55404 St. Paul, MN 55102

Trial of Late Surfactant to Prevent Bronchopulmonary Dysplasia

RESEARCH CONSENT FORM

INTRODUCTION

Before agreeing that you/your child will take part in this research study, it is important that you read and understand the following explanation. It describes the purpose, treatment plan, benefits, risks and discomforts of the study, and the safeguards that will be taken. It also describes the other options available and the right to withdraw from the study at any time.

BACKGROUND

You are being asked to take part in this study because your child was born prematurely and still needs a breathing machine (ventilator). If your child still needs assistance with breathing from the ventilator at 1 week of age, she or he will have a high risk of developing bronchopulmonary dysplasia (BPD), which is a condition where premature babies continue to have problems with their breathing and may require a ventilator and/or oxygen for many more weeks.

RESEARCH PURPOSE

The purpose of this multi-hospital study is to enroll 525 premature babies, who were born at less than 28 weeks’ gestational age and at increased risk for developing BPD due to their need for mechanical ventilation at 7 days of life. If enrolled in the study, all babies will receive a gas called inhaled nitric oxide (iNO), which is a routine therapy in our NICU for term infants with pulmonary hypertension. Nitric Oxide is a natural gas that is also made in the lungs. It opens the blood vessels that go to the lungs and improves development of the preterm lung. The study will randomize half the babies to receive additional surfactant to investigate if giving additional surfactant combined with iNO will improve their lung function and development. Surfactant is a natural product made in the lungs that is required for normal breathing.

RESEARCH PROCEDURES

If the screening of your child’s medical chart shows that your child can be in the study, we will review with you the “Inhaled Nitric Oxide Information Sheet.” In October 2010, the National Institutes of Health held a meeting to evaluate the research studies that gave iNO to premature babies. The panel found that there wasn’t enough support in these studies to recommend routine use of iNO in premature infants.

Your child will have a sample of his or her airway secretions collected. In order to collect airway secretions, a small amount of salt water is put into the breathing tube and then suctioned out and collected. If the addition of salt water is not advised dry suctioning will be used. Suctioning of the airway through the breathing tube is part of routine clinical care. We will try to collect the airway secretions for the study at the time your baby is due for routine clinical suctioning of the breathing tube. The airway secretions will be tested for surfactant function, as well as for various chemicals associated with lung inflammation. The samples will be labeled with your child’s study identification number only; your child’s name or birth date will not be used.Your child willbe "randomized" into one of the two study groups described below. Randomization means that your child is put into a group by chance, much like the flip of a coin. Neither you nor your child’s doctor can choose the group your child will be in. Your child will have an equal chance of being placed in either group.

Your child will be started on iNO gas therapy. The dose of gas will be lowered after 3-4 days, then once a week for the next three weeks, for a total of 3 ½ weeks, at which time it will be stopped completely. The gas therapy may be given either through the breathing tube or, if your child improves and the breathing tube is taken out, the iNO may be delivered through a nasal cannula.

If your child is in group 1, he or she will receive additional doses of the study drug, surfactant (Infasurf®). One dose will be given on the day of randomization. If your child continues to have the breathing tube in place to help with her or his breathing, your child will receive a dose of surfactant every 1 to 3 days for up to a total of 5 doses.

If your child has his or her breathing tube removed, your child will not receive a dose of surfactant. If the breathing tube is later replaced your child will return to the schedule described above, and the every 1 to 3 day schedule of dosing will be continued for a total of 5 doses. If a study drug dose is delayed because the doctors feel your child is not stable enough for the dose procedure, the dosing will be continued when your child’s condition improves, and a total of 5 study doses will be given.

When your baby receives the surfactant, screens will be placed around the bedside and you and the bedside caregivers will step away from the bedside for approximately 20 minutes. Your child will remain on all of her or his monitors used for routine clinical care. A nurse and respiratory therapist, who is trained and experienced in the administration of surfactant and the care of breathing tubes and mechanical ventilators, will give the surfactant and will monitor your infant during this time period. A physician or Neonatal Nurse Practitioner will be present in the Intensive Care Nursery during the procedure.

If your child is in group 2, he or she will not receive any additional treatment. Your child will have a “sham procedure” so that the study investigators will not know whether your child is in group 1 or group 2. For this “sham procedure,” the bedside caregivers will step away from the bedside for approximately 20 minutes and a nurse and respiratory therapist will be behind a screen with your baby as if they are giving surfactant, but no study drug will be given. Your child will remain on all of his or her monitors used for routine clinical care and a nurse and respiratory therapist will monitor your infant during this time period. This procedure will be repeated if your child continues to have the breathing tube in place to help with his or her breathing every 1 to 3 days up to a total of 5 additional “sham” doses. If your child has his or her breathing tube removed, this procedure will not be performed. If the breathing tube is later replaced, the procedure will happen at that time and then the dosing schedule will be continued as above.

Your child will have a sample of his or her airway secretions collected prior to each dose of surfactant or the “sham procedure.” Suctioning of the airway through the breathing tube is part of routine clinical care, and it is performed for clinical care before giving a dose of surfactant. Each time, the procedure will be the same as the procedure for the first collection of airway secretions. We will try to collect the airway secretions for the study at the time your baby is due for routine clinical suctioning of the breathing tube.

We will collect a sample of your child’s urine at the beginning of the study and three times a week for 4 weeks, then once a week until your baby reaches 36 weeks gestational age. To collect the urine, the nurse will place a cotton ball in your baby’s diaper. This is the routine way that the nurses collect urine from preterm babies when they need to do tests on the urine. The urine will be saved to test for chemicals associated with lung growth.

When your child has finished receiving additional surfactant or the “sham procedure” the study doctors will continue to monitor your child’s status until he or she is discharged from the hospital. The doctors will be looking at whether your child has a diagnosis of BPD at 36 weeks corrected gestational age (4 weeks before you original due date) and again at 40 weeks corrected gestational age (your original due date).

Before discharge, a member of the study team will meet with you to ask about family and home factors that are risks for wheezing and cough. We will also request contact information from you that will help us follow your child. Also, in order for us to track your baby for follow-up exams, we will ask that you provide us with contact information.

After discharge from the hospital, your child will be seen in the Neonatal Follow Up Clinic, where all premature babies that are discharged from the NICU are seen. The follow-up visits will occur at 1 year and again at about 22-26 months. During these visits, your child will undergo evaluations of his or her neurological development and lung function status. You will also be contacted every 3 – 4 months in the first 12 months to answer questions on your child’s pulmonary status. This will take about 15 – 20 minutes and can be completed by phone. Active participation in hospital is 12-16 weeks, data will be collected until discharge and you will be interviewed at that time. The pulmonary questionnaire and 2 follow-up visits are at 12 and 22-26 months corrected age. The time required for the study is 4 hours in hospital, pulmonary questionnaires is 1 hour total (20 minutes X 3) and 2 follow-up visits approximately 3 hours each.

RISKS

Your child may have side effects while in this study and will be watched carefully for any side effects. However, doctors don't know all the side effects that may happen. Side effects may be mild or very serious. Many side effects go away soon after your child stops receiving the study treatment or procedure.

A small number of infants receiving high doses of inhaled nitric oxide have had a condition that alters the oxygen carrying molecule in red blood cells (methemoglobinemia). When this happens, the tissues in the body don’t receive enough oxygen. This condition is not seen in the lower inhaled nitric oxide doses we are using in this study. If this condition occurs, it resolves by stopping the iNO therapy.

If your child is in group 1, the group that receives surfactant, it is possible that you child would have any of the following risks:

Temporary lowering of heart rate or oxygen level. These are temporary and are the same risks seen with the routine surfactant therapy given to your child immediately after birth.

Blockage of the breathing tube requiring inserting a new breathing tube; this is a rare side effect and happens less than 5% of the times that surfactant is given and is based on clinical experience.

A physician will be present in the NICU during the treatment incase a new breathing tube is needed.

If your child is in the group 2, there are no risks to the “sham procedure”. Your child will be monitored in usual way through this procedure.

Suctioning of the airway through the breathing tube is part of routine care and is often associated with brief periods of slowing of the heart rate or oxygen level. We will try to coordinate the secretion collection with this routine care.

Collecting urine with cotton balls place in your child’s diaper will not add additional risk to your child.

Randomization Risks: Your child will be assigned to a treatment group by chance, and the treatment she or he receives may prove to be less effective or to have more side effects than the other study treatment.

Unknown Risks: The procedures in this study may have side effects that no one knows about yet. The researchers will let you know if they learn anything that might make you change your mind about your child participating in the study.

BENEFITS

Taking part in this study may or may not make your child’s health better. While doctors hope additional surfactant plus inhaled nitric oxide will be more effective than inhaled nitric oxide alone at improving your child’s lung function and decrease your child’s risk of developing BPD, there is no proof of this yet.

If your child is in the group that receives additional surfactant and it proves to treat your child’s condition more effectively than inhaled nitric oxide alone, you may benefit from participating in the study, but this cannot be guaranteed.

ALTERNATIVES

Your other choice may include:

Getting standard treatment for your child’s condition. This means that, at Children’s Hospitals and Clinics of Minnesota, your baby will continue to receive his or her current therapy without any additional surfactant replacement. Some babies not enrolled in the study may receive inhaled nitric oxide per the neonatologist’s discretion.

Please talk to your doctor about your choices before deciding if your child will take part in this study.

HOW TO GET ANSWERS TO YOUR QUESTIONS:

You are encouraged to ask questions both before you agree to be in the study and also at any time you need information.

If you have any questions about this study please contact the researcher, Dr. Mark Mammel at 651-220-6261 in St. Paul and Dr. Ellen Bendel-Stenzel at 612-813-6288 in Mpls. If you participate in the study and have questions at a later date please also feel free to ask at any time.

If you have any questions about your rights as a research participant or any complaints that you feel you cannot discuss with the investigators, you may call Debra McKeehen, Children's Hospitals and Clinics of Minnesota IRB Administrator at 651-220-5818.

If you have any questions or concerns that you feel you would like to discuss with someone who is not on the research team, you may also call the Family Relations Liaison in St. Paul at 651-220-6888 and in Mpls. at 612-813-7393.

CONFIDENTIALITY

Records of patients enrolled in this research are private, and any knowledge that is gained that can be used to identify patients will not be given to anyone other than University of California San Francisco (UCSF), the study sponsor, the IRB, and Government agencies, such as the Food and Drug Administration (FDA) and the National Institutes of Health (NIH). Knowledge that is gained from this study may be published in scientific journals without identifying the patient. Data collected will be kept in a secure de-identified database at UCSF. Your baby will be identified by a study identification number only. Neither your name nor your child's name will be in the database. The database can be accessed only by the study investigator who maintains it.