A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
DEXMEDETOMIDINE Study Basics
The purpose of this study is to figure out safe doses of a medicine called dexmedetomidine for babies having heart surgery. We also want to learn how long the medicine stays in the body, and how infants’ bodies absorb and get rid of this medicine (This is called pharmacokinetics). This is an important step in learning what the best dose of dexmedetomidine should be for infants.
The study will be done at three Pediatric Heart Network centers. About 100 – 200 patients across the centers will be enrolled in this study over about 36 months.
Who can be in the study?
This is study is for males or females 180 days old, and who have a diagnosis of different types of cardiac anomalies such as D-transposition of the great arteries (with or without
ventricular septal defect), or tetralogy of Fallot, or ventricular septal defect (with or without associated atrial septal defect and/or patent ductus arteriosus, and are scheduled for surgery for a heart condition.
What do we have to do to be in the study?
The study will be explained to you in detail by one of the study investigators. Once your questions have been answered, you will be asked to sign an informed consent form to enter the study.The study will be done in two parts. In the first part of this study, 10 groups of 7 children each will receive carefully determined doses of dexmedetomidine, starting in the operating room and continuing after surgery in the intensive care unit (ICU). These doses are all based on what we know from other studies in patients and are adjusted to the weight of your child. The first group will receive a very low dose of dexmedetomidine. Once we learn that the low dose is safe, the next group of children will receive a slightly higher dose of dexmedetomidine. The doses in the next groups will go up or down a little bit depending on the drug response in the earlier groups. Based on what we learn from these groups, a dosing schedule will be developed for low, medium, and high doses, using a computer program that takes into account a child’s age, weight, time of surgery, and other information. What we learn from your child’s doses will help us figure out this schedule.In the second part of this study, children will get the dexmedetomidine doses that have been carefully developed and reviewed by doctors during the first part of the study, to make sure that the dosing schedule is proper. We will tell you what dose of dexmedetomidine your child will be getting, and which part of the study your child is in.
- Before surgery: If you choose for your child to be in this study, your child will have the same tests and procedures that all children have here before they have heart surgery. No extra blood samples will be needed before surgery. There will be nothing different during this phase if your child is involved in the study.
- During surgery: During your child’s heart surgery, doctors use a machine to help circulate blood around the body called a heart lung bypass machine. For the study, a doctor will be giving dexmedetomidine into this machine. This machine also helps deliver other medicines to your child during the surgery, and for the study, and that is why your child will get dexmedetomidine this way. Dexmedetomidine will also be given to most children in the study through their IV before the start of the surgery, and after coming off the heart lung bypass machine. Besides dexmedetomidine, your child will also receive standard medicines for anesthesia, including anesthetic gas and medicine through his/her IV, to make sure he/she is completely asleep and won’t feel pain during surgery. To measure how much dexmedetomidine is in your child’s blood, doctors or nurses will take small amounts of blood at regular time periods during the surgery. To get blood samples, we will use one of the small, plastic tubes (catheters) that your child will already have in place, so your child will not have any extra needle sticks.
- After surgery: Your child will be transferred to the ICU for close monitoring, as is the case for all babies after heart surgery. Most babies in the study will continue to receive doses of dexmedetomidine for the first 6 to 12 hours after surgery. Your child will also receive other medicines as needed to treat pain and anxiety, to make sure he/she is as comfortable as possible after surgery. To measure how much dexmedetomidine is in your child’s blood, nurses will draw small amounts of blood while your child is getting dexmedetomidine and for about 24 hours after the medicine is stopped. To get blood samples, we will use one of the small, plastic tubes (catheters) that your child will already have in place, so your child will not have any extra needle sticks. The total amount of blood needed for all testing in the operating room and ICU will be approximately 3 to 4 teaspoons (15-20 ml), depending on your child’s weight. Your child will be monitored closely both during and after surgery.
Your child’s vital signs (including heart rate, blood pressure, breathing rate, temperature, and oxygen level in the blood) will be monitored after the surgery. For this study, this information will be recorded while your child receives dexmedetomidine and for 24 hours after the medicine is stopped. Your child's vital signs will continue to be monitored after this; but this information will not be collected for this study. The monitoring your child will get will be the same as the usual care that is given after this type of heart surgery.The study doctor may take your child out of the study at any time and for any reason.
Some of the reasons the doctor may take your child out of the study include:
- Your child’s condition worsens
- The study is stopped
- The study drug is no longer available
- Your child cannot meet all the requirements of the study
- New information suggests taking part in the study may not be in your child’s best interests
- You decide to take back your permission for us to collect, use or share your child’s health information. This will not affect your child’s care in any way.
Study personnel will be in contact with you during the time you are in the study. You are free to call the nurse or study coordinator at any time with any questions or concerns that you may have.
How long will we be in the study?
There will be a Study Enrollment Visit where the PI, Study Coordinator, or other research staff will present the study to the parent/guardian and obtain written informed consent to conduct a full eligibility screening. This will occur in the hospital for inpatients, or in the preoperative clinic for outpatients. Study enrollment will occur only after full eligibility is confirmed.
The only other study visit is the Perioperative Period. It begins with entrance into the operating room, and data collection ends 24 hours after the dexmedetomidine infusion is discontinued. A final assessment for Adverse events will occur at the earliest of 30 days after dexmedetomidine infusion is discontinued or the date of withdrawal from study. There are no additional follow-up visits or assessments.
What are the possible benefits to being in this study?
One of the benefits (good things) of this study may be that your child has good control of his/her pain and remains sleepy without a change in his/her breathing, making it easier to be taken off the breathing machine. Your child may also have the breathing tube removed earlier and be more comfortable than with the usual medicines. Your child may also need fewer medicines for anesthesia or for pain and anxiety to make him/her comfortable. On the other hand, how well dexmedetomidine works is not yet fully known in newborns and young infants, which is why we are doing this study, so it may be that your child will not be helped by taking part in this study. The information we learn may help children with similar conditions in the future.
What are the possible risks to being in this study?
- Taking part in a research study involves risks or “side effects.” You should talk about these risks with the study doctor or your child’s regular doctor. There may be other side effects we do not know about yet. We may give your child other medicines to make any side effects less serious or to make your child feel better.
- Your child will start to receive one of five doses of dexmedetomidine in the operating room. The best dose for newborns and young infants is not yet known. The first group of 7 children will receive a low dose. Once we learn that dose is safe to give, the next group of 7 children will receive a slightly higher dose of dexmedetomidine. The higher doses may work better but may have a higher chance of side effects, while the lower doses may not work as well but may have a lower chance of side effects. There might not be any difference between the doses.
- The most common side effect of dexmedetomidine is a decrease in blood pressure. Less common side effects include slowing of the heart rate and sleepiness. We continuously monitor blood pressure, heart rate, and level of sleepiness after surgery.
- The most serious side effects of dexmedetomidine that are rarely seen in children are a severe change in the rhythm of the heart (arrhythmia), a slowing of the heart beat, and very low blood pressure. Although rare, these side effects could be life threatening and possibly require cardiopulmonary resuscitation (CPR), or use of ECMO—a machine to take over the function of the heart. And, we know that children having this type of surgery can have these serious things happen even without dexmedetomidine. Your child will be closely monitored while receiving this and other medications in the operating room and ICU. Dexmedetomidine will be stopped right away if any serious side effects occur that could be caused by the medicine.
- Your child may need more anesthesia or medicine for pain and anxiety even after receiving dexmedetomidine. The doctors and nurses caring for your child will be watching to see if your child needs more anesthesia in the operating room or more medicine for pain and anxiety in the ICU. If your child needs more anesthesia or medicine for pain and anxiety, the doctors will give additional medicines. These are the same medicines your child would receive if she/he were not involved in this study.
- As with any medicine, your child may be allergic to dexmedetomidine and develop a rash, itching, and/or swelling. If this happens, the doctors may give another medicine to treat the allergy. If the dexmedetomidine infusion is still running, it will be stopped right away.
- Since blood will be taken from a catheter that is already in place or at the same time as other blood tests that your child’s doctor has ordered are being drawn, there should be no additional risk from the taking of blood samples. The amount of blood taken for this study is small.
- There may be risks to being in this study that we don't know about now. You will be informed of any changes in the way the study will be done and any additional risks identified.
What are the costs to me to be in the study?
There will be no extra costs to you when you join this study. You must pay for all other costs related to your normal medical care such as hospital stays, surgery, drugs, lab tests, and doctor's fees which are thought to be standard medical care for patients with your condition.