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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
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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.
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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.
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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.
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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 651220-6888 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.
The secretions collected from your child’s breathing tube and the urine samples will be stored in
a tissue bank and analyzed at the UCSF. There will be no patient identifiers other than the study
number and date collected on these samples. The samples will be stored indefinitely, until it is
used up or destroyed. Your child’s sample may be used to develop new drugs, tests, treatment or
products. Participation is this extra research is voluntary, and if you choose not to allow the extra
research it will in no way affect your child’s care in the current study. You may at any time
contact Dr. Mammel or Dr. Bendel-Stenzel by mail or telephone to ask that your child’s samples
be withdrawn from additional research use and those samples will be destroyed.
FINANCIAL ISSUES
Costs for participation in study
Your child will not be charged for the study activities. The research study, funded by the
NHLBI/NIH, will provide support for the staff who will carry out the study and collect samples
and data from the study. The study drug (surfactant) will be provided by ONY Inc. Ikaria Inc.,
the manufacturer of inhaled nitric oxide, is providing inhaled nitric oxide for this study. All of
your child’s regular care, including the inhaled nitric oxide if used before entering the study, will
be billed to you or your insurance carrier.
Will my child be paid for taking part in this study?
Your child will not be paid for taking part in this study. Your child will receive a token gift
valued at less than $7.00 with a thank you note attached.
OTHER INFORMATION:
You have been told about the treatment plan, including those parts that are investigational, about
the side effects and benefits to be expected, and have had the other choices described to you.
Taking part in this research is completely voluntary. By signing this Consent Form, you agree to
take part in this research study. You are free to withdraw from this research study at any time
without prejudice of any kind. If you have any questions at any time, they will be answered. If
you choose not to take part, you will still be offered the best care for the patient's needs.
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In the event that this research activity results in an injury, please contact Mark Mammel, MD at
651-220-6261 in St. Paul or Dr. Bendel-Stenzel at 612-813-6288 in Mpls. Treatment will be
available, including first aid, emergency treatment and follow-up care as needed. Payment for
any such treatment must be provided by you or your third party payer, if any (such as health
insurance, Medicare, etc.). By signing this Consent Form, you are not waiving any rights that you
otherwise may have. In the event that you are not covered by insurance please call the patient
relations liaison at 612-813-7393, who will help you with your rights.
Should the disease become worse, should side effects become severe, should new information
become known or should your doctor feel this treatment is no longer what is best for the patient,
your participation in this study may be stopped and other options discussed.
Any significant new findings that may develop during the course of the research and might
impact your willingness to continue participation in the study, will be provided to you by the
study investigator.
Optional Biologic Studies: All airway secretions and urine collected for the purposes of this
study will be used to learn more about the lungs of premature babies for purposes of research.
Airway secretions and urine that are collected will be stored so all the samples can be analyzed
together. If some of the samples remain after this study is completed, instead of discarding your
child’s leftover specimen it will be saved in a “tissue bank” for future additional studies of the
premature lung, based on information gained from this and other research.
In some cases, it is possible to collect genetic material (DNA) from the airway secretions that are
collected as part of this study. There is some information that bronchopulmonary dysplasia and
the response to treatments for bronchopulmonary dysplasia may be related to genetics (diseases
that are passed on in families). If genetic material is collected from your child’s airway
secretions, it could be stored in the tissue bank and used for genetic research to understand better
the premature lung and other conditions that affect premature babies. If your child’s specimen is
used for genetic research, this information will not become part of your child’s medical record.
Since these tests are being done for research purposes, the significance of results may not be
known for many years. Reports about any research studies will not be given to you or your
child’s doctor. If you have further questions regarding participation in this genetic research,
please ask for and refer to the handout, “Genetic Research: Issues to Consider.” Please indicate
whether you are willing to allow this genetic research by initialing one of the lines at the end of
the form. The genetic material will only be identified by your child’s study number, and it will be
maintained separately from other information about your child in the same way that the leftover
airway secretions and urine are maintained separately.
The tissue bank is located in the lung development laboratory of Dr. Philip Ballard in the
Department of Pediatrics at UCSF. Your child’s specimen will be kept indefinitely, until it is
used up or destroyed. The specimen and certain medical information about your child may be
given to other scientists at UCSF or other collaborators not at UCSF, but your child’s name,
address, phone number, or any other information that would identify her or him will not be shared
with anyone. Genetic information may be stored in a research database accessible to qualified
medical researchers that will not contain any identifying information about your child. Genetic
samples may be used for genome-wide studies, which are studies of all genetic variation in
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humans. Your child’s specimen may be used to develop new drugs, tests, treatments or products.
In some instances these may have potential commercial value. You or your child will not be paid
or receive money, if this is the case. Participation in this extra research is voluntary, and if you
choose not to allow the extra research it will in no way affect your child’s care in the current
study. You may at any time contact Dr. Mammel in St. Paul or Dr. Bendel-Stenzel in
Minneapolis. by mail or telephone to ask that your child’s samples be withdrawn from additional
research use, and any identifiable samples still in the researcher’s possession will be destroyed.
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Please indicate whether you are willing to allow extra research on the lungs of premature
babies from your child’s airway secretions and urine by initialing one of the lines below:
_____I do not want my child’s airway secretions and urine used for any research or tests
other than those needed for the current research study.
_____The investigators may keep my child’s extra airway secretions and urine for future
research on the lungs of premature babies.
Please indicate whether you are willing to allow genetic research on lungs of premature
babies in the future from your child’s genetic material, which will be confidentially banked
indefinitely by the researchers, by initialing one of the lines below:
_____I do not want my child’s genetic material (DNA) used for any research or tests.
_____The investigators may use my child’s genetic material (DNA) for future research
on the lungs of premature babies.
Please indicate whether you are willing to be contacted about having your child participate
in future studies by initialing one of the lines below:
_____ I do not want to be contacted about future research.
_____ The investigators may contact me about future research.
Your signature below means that you have read the above information, that you have
discussed this study with your doctor and his or her staff, and that you have decided to take
part based on what you have read and discussed.
You will be provided a copy of this form.
Parent/Guardian Signature
Date
Parent/Guardian Signature
Date
I have fully explained this research study to the participants, and in my judgment there was
sufficient information regarding risks and benefits, to make an informed decision. I will inform
the participant in a timely manner of any changes in the procedure or risks and benefits if any
should occur.
Researcher's Signature
IRB #: 1002-015
Consent Version 3.1
Date
IRB Approval Date: 3/22/2010
Consent Version 3.1 approved: 3/08/2011
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