The TEAMMATE trial is a clinical research study led by Stanford Children’s Hospital and Boston Children’s Hospital, and funded by the US Department of Defense. Over 200 children and young adults at 25 hospitals around the United States will enroll in the TEAMMATE trial.
Why are we doing the TEAMMATE trial?
The goal of the study is to figure out which medicines to prevent heart rejection work best and have the fewest side effects. Today, the average survival after pediatric heart transplant is about 15 years, and is limited to 15 years by several common problems.
- Rejection (two different types, cellular and antibody)
- Coronary artery disease
- Kidney disease
- A form of cancer called post-transplant lymphoproliferative disease (PTLD)
Transplant Cardiologists prescribe anti-rejection medicines to children after heart transplant to keep the body’s immune system from attacking the new heart and to also help minimize these common problems. Anti-rejection medicines are used all the time after heart transplants, but no anti-rejection medication has been approved by the Food and Drug Administration (FDA) for use in children after heart transplant.
TEAMMATE will compare the effects of two combinations of anti-rejection medicines in children and young adults who have had a heart transplant. The first combination of medicines is everolimus (or Zortess®) and low-dose tacrolimus (or Prograf®). The second combination of medicines is standard-dose tacrolimus (or Prograf®) and mycophenolate mofetil (or Cellcept®).
The primary goal of the TEAMMATE trial is to figure out which combination of medicines is better at preventing long-term problems after heart transplant. The problems we are most concerned about are rejection, kidney problems, coronary artery disease, infection, and PTLD.
We hope that data from the TEAMMATE trial help researchers figure out which anti-rejection medicines prevent transplant complications, and lead to the first FDA approval of anti-rejection medicines in pediatric heart transplantation.
Children eligible for this study must be less than 21 years of age at the time of heart transplant. Children may enroll when they reach 4-7 months after heart transplantation. Eligible children must not have any active or ongoing serious problems like rejection or infection. More specific details about criteria for participation is available on the clinicaltrials.gov website, which you can find by clicking here.
If you or your child is eligible, the study will be explained to you or your child in detail by one of the study investigators. Once your questions have been answered, you or your child will be asked to sign an informed consent form to enter the study. The study has four major parts:
Screening: Children eligible for this study must be less than 21 years of age at the time of heart transplant. Children may enroll when they reach 4-7 months after heart transplantation. Eligible children must not have any active or ongoing serious problems like rejection or infection. More specific details about criteria for participation is available on the clinicaltrials.gov website, which you or your child can find by clicking here.
Randomization: If eligible after screening, you or your child will be randomly assigned to receive tacrolimus and Cellcept (MMF) or tacrolimus and everolimus. The assignment is done by chance, like flipping a coin. About half of the children in this study will be assigned to receive tacrolimus and MMF; the other half will be assigned to receive tacrolimus and everolimus.
Conversion to Tacrolimus and Everolimus: Children who are already on tacrolimus and MMF who are assigned to tacrolimus and MMF, will continue to take the same medications. Children who are assigned to tacrolimus and everolimus will be converted from MMF to everolimus using a standard protocol. This transition will take approximately one week. Regardless of which drug combination you or your child is assigned, testing for several additional drug levels will be required during the first week.
Follow up: You or your child will be closely monitored while on either drug regimen. During this time, the study team will assess how well you or your child is doing through physical exams, laboratory tests, medical support, questionnaires, and other tests, up until right before through the end of the study. In general, all the study visits take place at the same time as routine post-transplant care, so additional study visits are not required.
You or your child’s participation is 30 months, when the final study visit (of 8) will occur.
Benefits of Trial
You or your child may not receive any benefits from being in this study.
You or your child may have relatively few transplant adverse events regardless of the drug regimen you or your child is assigned to.
If you or your child is assigned to receive tacrolimus and MMF, the benefits include having you or your child receive a medical regimen that has been used in several thousand children already. Although this regimen is not FDA-approved for heart transplant in children, it is FDA-approved for pediatric liver and kidney transplant, and adult heart transplantation.
If you or your child is assigned to tacrolimus and everolimus, the benefits may include fewer transplant complications, and specifically it may reduce rejection, coronary artery disease, and kidney disease. These complications are linked to reduced graft survival. This drug regimen is also not FDA-approved for pediatric heart transplantation, but is approved for pediatric liver and kidney transplant, and is approved for adult heart transplantation in Europe.
Taking part in a research study involves risks, or side effects. You or your child should discuss these risks with you or your child’s study doctor. Children eligible for this study all have a serious heart condition (heart transplant) whether or not they choose to participate in this study.
The risks of the transplant medications include infection, kidney problems, infection, diabetes, high blood pressure, and abdominal symptoms like belly pain and nausea. A complete list of the risks is provided in the informed consent form and will be explained in full by the study doctor. There may be additional risks that are not yet known. If any new risks are identified, the study doctor will share those with you.
Throughout the study, you or your child’s health and safety will be monitored by the study doctor. Additionally, an independent board of scientists and medical professionals with expertise in areas such as adult and pediatric hear transplantation will regularly review study data and make recommendations to the Department of Defense regarding patient safety in this trial. Stringent safety reporting to the FDA is also required for this trial.
Why should you be part of the TEAMMATE Trial?
- TEAMMATE is the first randomized study comparing anti-rejection medications in children who have received a heart transplant.
- The results of this trial will help doctors learn what drugs are the safest and best at preventing rejection in kids who have had a heart transplant.
- The results from the study may lead to the first FDA approval of anti-rejection medications for use in kids who have had a heart transplant, which will make these medications easier to prescribe.
- Participants will receive a small payment of $50 per visit to help cover out of pocket expenses (travel, meals, etc.).
TEAMMATE Trial Updates
- We have enrolled at over 20 clinical sites.
- Over 200 patients have been enrolled in the trial and have been “randomized” to one of the two treatment arms.
- We have enrolled and randomized a total of 211 pediatric heart transplant recipients. Enrollment is now complete.