After more than a decade of work, the Tracheal Occlusion To Accelerate Lung Growth (TOTAL) Trial was published. This trial showed a survival benefit for fetuses with very high-risk Congenital Diaphragmatic Hernia (CDH) who underwent the Fetoscopic Endoluminal Tracheal Occlusion (FETO) procedure. In the ongoing effort to provide optimal care for patients, The Fetal Center, affiliated with Children’s Memorial Hermann Hospital, McGovern Medical School at UTHealth, and UT Physicians, has been offering FETO for the prenatal treatment of CDH through participation in both the Severe and Moderate Arms of the TOTAL Trial.
As a recognized, international leader in the prenatal diagnosis and management of CDH, Anthony Johnson D.O., Co-Director of The Fetal Center, worked closely with Professor Deprest (the study’s lead author and principle investigator) to lead the process of bringing the trial to the U.S., enrolling and managing these patients, and co-authoring the publications in the New England Journal of Medicine. As one of only 10 U.S. fetal centers granted FDA to offer FETO intervention and the only fetal center in the U.S. to participate in both arms of the TOTAL Trial, the Comprehensive Center for CDH Care and the entire team at UTHealth and Children’s Memorial Hermann Hospital are actively engaged and dedicated to improving outcomes for all patients with CDH – mild, moderate, or severe.
Selected Podcast
TOTAL Trial Results for CDH Patients with Dr. Anthony Johnson
Featuring:
He received his medical degree from the West Virginia School of Osteopathic Medicine in Lewisburg, West Virginia, and subsequently completed his fellowship in Maternal-Fetal Medicine at Pennsylvania Hospital in Philadelphia and a fellowship in medical genetics at Thomas Jefferson University Hospital in Philadelphia. He later served as the director of the Fetal Intervention Program in the Division of Maternal Fetal Medicine at North Carolina Women's Hospital in Chapel Hill, North Carolina prior to relocating to Houston in 2006.
Anthony Johnson, DO
Dr. Anthony Johnson is an internationally renowned specialist in maternal-fetal medicine (MFM). He has performed more than 400 laser ablation procedures in the treatment of severe twin-to-twin transfusion syndrome, and has extensive experience with other fetoscopic-based and needle guided in utero procedures.He received his medical degree from the West Virginia School of Osteopathic Medicine in Lewisburg, West Virginia, and subsequently completed his fellowship in Maternal-Fetal Medicine at Pennsylvania Hospital in Philadelphia and a fellowship in medical genetics at Thomas Jefferson University Hospital in Philadelphia. He later served as the director of the Fetal Intervention Program in the Division of Maternal Fetal Medicine at North Carolina Women's Hospital in Chapel Hill, North Carolina prior to relocating to Houston in 2006.
Transcription:
Caitlin Whyte (Host): Advancing health, personalizing care at Memorial Hermann, this is our mission. This podcast shares the science and stories behind those efforts. Today we're interviewing Dr. Anthony Johnson to discuss the recently published results of the TOTAL trial, a landmark trial to advance care for patients with CDH.
This is Advance, the podcast series from Memorial Hermann. I'm Caitlin Whyte. As we know, Doctor, a landmark research trial focused on patients with congenital diaphragmatic hernia or CDH was recently published in the New England Journal of Medicine. Can you tell us a little bit about this trial and about the purpose of the trial?
Anthony Johnson, DO (Guest): Sure happy to. The trial is called the Tracheal Occlusion To Accelerate Lung Growth. Or the TOTAL trial. It was an international multicenter randomized trial with two arms, the severe arm and the moderate arm. And it was basically put into play to evaluate survival and morbidity in fetuses with a congenital diaphragm hernia, or CDH.
The difference between the two arms, the severe arm was based on lung volume, if you will. All right, the severe arm would have a less lung volume available and those patients underwent fetal intervention, or randomized to fetal intervention at less than 30 weeks or roughly less than seven months. And the moderate arm was looking at not just survival, but also long-term morbidity in the neonates and children.
And that's the randomization there resulted in the intervention between 30 and 32 weeks or seven to seven and a half months. The purpose of the trial was really trying to advance the care and understanding and improve the outcomes for children with CDH.
Host: And what were the findings of the TOTAL Trial?
Dr. Johnson: The trial, ten years in completion, found that the severe group actually benefited from fetal intervention when the surgeries were done between 27 and 30 weeks gestation. It improves survival with reduced morbidity in those children.
And that, that improved outcome actually extended not just in the newborn period, but actually up until six months of age. That's as far as we followed them right now. So, we're still looking at the long-term outcome. The moderate arm, when the procedures were done at 30 to 32 weeks or seven to seven and a half months, didn't show an improvement. Both studies though showed that the babies that went through intervention had an increased risk for premature delivery, preterm labor, and premature rupture of membranes. So, it's kind of a balancing act between the two.
Host: Now, just how were you and your organization involved in the TOTAL trial?
Dr. Johnson: I been working with Professor Deprest, the principal investigator of the trial for the past 11 years in this endeavor. Part of our undertaking was trying to incorporate other US centers into the trial to participate.
So, my role was not only as a local co-investigator, but also I was a coordinator of the 10 sites, and in North America that moved forward to get this endeavor underway. Of the sites, one was in Canada, nine were in the US. We needed to get FDA approval to move forward with this. So, I was paramount in helping that happen.
And then from there coordinated things forward. Our program here at Children's Memorial Hermann Hospital was the only fetal center to participate in both arms of the TOTAL trial.
Host: Wow. And has your multiple disciplinary team been involved in other research efforts for CDH?
Dr. Johnson: When I joined the team here roughly 10 years ago, it was based on the work that's being done with CDH, a significant part of that. The program here is amazing with regard to the affiliated teams and basic translational and the clinical scientific work in this area, trying to advance what we need to know and what the new therapies might be. The team here, really is amazing. It leads investigative collaboration internally and also with associated sites. In the past two years alone, there's been over 40 peer review publications coming out in CDH. Fortunately, just before the COVID outbreak here, we were able to sponsor the International Congenital Diaphragm Hernia Symposium. It's an educational program to advance our knowledge in this disorder with 11 different countries participating.
We're constantly moving forward to try and striving to learn more about how to help patients in this area with our expertise. Right now we're the only center that I'm aware of, that's actually looking at the use of stem cells in a phase one trial for the treatment of CDH.
Host: Can you tell us just how you and your multidisciplinary team care for patients with CDH?
Dr. Johnson: Yeah. You know, anything you do in the fetal world has to have a postnatal team. I mean, we can do a lot of things here, but if we don't have somebody on the other side of the delivery, that's ready to run with this, you're really just kidding yourself. And that's one of the amazing things about the group here. There's over 30 years of experience with CDH in this center. It's a national referral center for CDH. It's a multidisciplinary team that starts just in the prenatal side with the maternal fetal medicine specialists, neonatologists, pediatric surgeons, pediatric anesthesiologists, and other pediatric specialists.
And it's all integrated together but between UTH and Children's Memorial Hermann Hospital to really provide quality care. And this diagnosis, again, being full nondisclosure as to what we're doing, what the patient's still going to experience moving forward to make it a smooth transition. The beauty about things here, we start before delivery pre-Apgar, if you will, all the way through to adulthood taking care of these people. It's really based on just an understanding of how this is going to move forward. And part of that process has been able to allow us have a higher than expected risk stratified survival rate. One of the highest in the world.
Host: Now, will your center be offering the fetal procedure to CDH patients?
Dr. Johnson: Moving forward. Yes, we will. For those patients that qualify. The evidence shows that there's definitely benefit. Okay. And we will continue to advance this looking at different modifications in this. We're going to continue to collaborate with the centers that have been working with this to move forward.
We're working with manufacturing and the FDA to see how we might be able to move this forward into the US. With a comprehensive program, we feel confident we can continue to provide expertise in this area and sort of tailor the management. We're looking at actually introducing this technology into newer populations that have additional funds that would have been excluded in the original trial.
The team's committed to providing the specialty care to families with CDH. We're all about the patient. Okay. Making it convenient. We know they're anxious when they have these diagnoses. So, we make ourselves pretty much 24/7, not actually to the physician to help get the referral here, but actually to the patient, telling them what to expect when they come in.
Sometimes that's, you know, they're a far distance away and we received referrals from some 39 different states. So, it can be virtual. Picking up the phone, happy to call you. This is my cell phone number. Just please let us know if we can help. That's part of what we do because we know they're overwhelmed and we want to sort of calm it down. We can help them.
Host: Talking more about moving forward, what are the next steps in CDH research?
Dr. Johnson: Well, one of the things is going back and looking at a re-evaluation of the moderate arm. One of the big differences between that and the severe is when the procedure was done and looking at some of the preliminary information that would suggest that this moderate group actually may still show benefit if we back the procedure down. IN other words, treating them all at the same time at that 27 to 29 weeks. There's some other ongoing work looking at different modifications of the device that we might be able to minimize risk to the mother by changing the procedure, so that she doesn't undergo two procedures when she's having this fetal intervention and seeing if we can go back and reanalyze the US data to find a way that will sort of standardize things moving forward and helping other centers move forward and allowing patients to have access to this device.
Host: Great. Well, Doctor, where can we find out more information about this trial and your program?
Dr. Johnson: Sure. Online, you can go to the Memorialherman.org/totaltrial, or you can give us a call 832-325-7288.
Caitlin Whyte (Host): Well, thank you Doctor for your time, and for this information today. To learn more or to refer a patient, visit Memorial hermann.org/total trial.
That's Memorial Hermann, H-E-R-M-A-N-N.org, or call 832-325-7288. That's 832-325-7288. If you found this podcast helpful, please share it on your social channels and be sure to check out the entire podcast library for topics of interest to you. This has been Advance, the podcast series from Memorial Hermann. I'm Caitlyn Whyte. Stay well.
Caitlin Whyte (Host): Advancing health, personalizing care at Memorial Hermann, this is our mission. This podcast shares the science and stories behind those efforts. Today we're interviewing Dr. Anthony Johnson to discuss the recently published results of the TOTAL trial, a landmark trial to advance care for patients with CDH.
This is Advance, the podcast series from Memorial Hermann. I'm Caitlin Whyte. As we know, Doctor, a landmark research trial focused on patients with congenital diaphragmatic hernia or CDH was recently published in the New England Journal of Medicine. Can you tell us a little bit about this trial and about the purpose of the trial?
Anthony Johnson, DO (Guest): Sure happy to. The trial is called the Tracheal Occlusion To Accelerate Lung Growth. Or the TOTAL trial. It was an international multicenter randomized trial with two arms, the severe arm and the moderate arm. And it was basically put into play to evaluate survival and morbidity in fetuses with a congenital diaphragm hernia, or CDH.
The difference between the two arms, the severe arm was based on lung volume, if you will. All right, the severe arm would have a less lung volume available and those patients underwent fetal intervention, or randomized to fetal intervention at less than 30 weeks or roughly less than seven months. And the moderate arm was looking at not just survival, but also long-term morbidity in the neonates and children.
And that's the randomization there resulted in the intervention between 30 and 32 weeks or seven to seven and a half months. The purpose of the trial was really trying to advance the care and understanding and improve the outcomes for children with CDH.
Host: And what were the findings of the TOTAL Trial?
Dr. Johnson: The trial, ten years in completion, found that the severe group actually benefited from fetal intervention when the surgeries were done between 27 and 30 weeks gestation. It improves survival with reduced morbidity in those children.
And that, that improved outcome actually extended not just in the newborn period, but actually up until six months of age. That's as far as we followed them right now. So, we're still looking at the long-term outcome. The moderate arm, when the procedures were done at 30 to 32 weeks or seven to seven and a half months, didn't show an improvement. Both studies though showed that the babies that went through intervention had an increased risk for premature delivery, preterm labor, and premature rupture of membranes. So, it's kind of a balancing act between the two.
Host: Now, just how were you and your organization involved in the TOTAL trial?
Dr. Johnson: I been working with Professor Deprest, the principal investigator of the trial for the past 11 years in this endeavor. Part of our undertaking was trying to incorporate other US centers into the trial to participate.
So, my role was not only as a local co-investigator, but also I was a coordinator of the 10 sites, and in North America that moved forward to get this endeavor underway. Of the sites, one was in Canada, nine were in the US. We needed to get FDA approval to move forward with this. So, I was paramount in helping that happen.
And then from there coordinated things forward. Our program here at Children's Memorial Hermann Hospital was the only fetal center to participate in both arms of the TOTAL trial.
Host: Wow. And has your multiple disciplinary team been involved in other research efforts for CDH?
Dr. Johnson: When I joined the team here roughly 10 years ago, it was based on the work that's being done with CDH, a significant part of that. The program here is amazing with regard to the affiliated teams and basic translational and the clinical scientific work in this area, trying to advance what we need to know and what the new therapies might be. The team here, really is amazing. It leads investigative collaboration internally and also with associated sites. In the past two years alone, there's been over 40 peer review publications coming out in CDH. Fortunately, just before the COVID outbreak here, we were able to sponsor the International Congenital Diaphragm Hernia Symposium. It's an educational program to advance our knowledge in this disorder with 11 different countries participating.
We're constantly moving forward to try and striving to learn more about how to help patients in this area with our expertise. Right now we're the only center that I'm aware of, that's actually looking at the use of stem cells in a phase one trial for the treatment of CDH.
Host: Can you tell us just how you and your multidisciplinary team care for patients with CDH?
Dr. Johnson: Yeah. You know, anything you do in the fetal world has to have a postnatal team. I mean, we can do a lot of things here, but if we don't have somebody on the other side of the delivery, that's ready to run with this, you're really just kidding yourself. And that's one of the amazing things about the group here. There's over 30 years of experience with CDH in this center. It's a national referral center for CDH. It's a multidisciplinary team that starts just in the prenatal side with the maternal fetal medicine specialists, neonatologists, pediatric surgeons, pediatric anesthesiologists, and other pediatric specialists.
And it's all integrated together but between UTH and Children's Memorial Hermann Hospital to really provide quality care. And this diagnosis, again, being full nondisclosure as to what we're doing, what the patient's still going to experience moving forward to make it a smooth transition. The beauty about things here, we start before delivery pre-Apgar, if you will, all the way through to adulthood taking care of these people. It's really based on just an understanding of how this is going to move forward. And part of that process has been able to allow us have a higher than expected risk stratified survival rate. One of the highest in the world.
Host: Now, will your center be offering the fetal procedure to CDH patients?
Dr. Johnson: Moving forward. Yes, we will. For those patients that qualify. The evidence shows that there's definitely benefit. Okay. And we will continue to advance this looking at different modifications in this. We're going to continue to collaborate with the centers that have been working with this to move forward.
We're working with manufacturing and the FDA to see how we might be able to move this forward into the US. With a comprehensive program, we feel confident we can continue to provide expertise in this area and sort of tailor the management. We're looking at actually introducing this technology into newer populations that have additional funds that would have been excluded in the original trial.
The team's committed to providing the specialty care to families with CDH. We're all about the patient. Okay. Making it convenient. We know they're anxious when they have these diagnoses. So, we make ourselves pretty much 24/7, not actually to the physician to help get the referral here, but actually to the patient, telling them what to expect when they come in.
Sometimes that's, you know, they're a far distance away and we received referrals from some 39 different states. So, it can be virtual. Picking up the phone, happy to call you. This is my cell phone number. Just please let us know if we can help. That's part of what we do because we know they're overwhelmed and we want to sort of calm it down. We can help them.
Host: Talking more about moving forward, what are the next steps in CDH research?
Dr. Johnson: Well, one of the things is going back and looking at a re-evaluation of the moderate arm. One of the big differences between that and the severe is when the procedure was done and looking at some of the preliminary information that would suggest that this moderate group actually may still show benefit if we back the procedure down. IN other words, treating them all at the same time at that 27 to 29 weeks. There's some other ongoing work looking at different modifications of the device that we might be able to minimize risk to the mother by changing the procedure, so that she doesn't undergo two procedures when she's having this fetal intervention and seeing if we can go back and reanalyze the US data to find a way that will sort of standardize things moving forward and helping other centers move forward and allowing patients to have access to this device.
Host: Great. Well, Doctor, where can we find out more information about this trial and your program?
Dr. Johnson: Sure. Online, you can go to the Memorialherman.org/totaltrial, or you can give us a call 832-325-7288.
Caitlin Whyte (Host): Well, thank you Doctor for your time, and for this information today. To learn more or to refer a patient, visit Memorial hermann.org/total trial.
That's Memorial Hermann, H-E-R-M-A-N-N.org, or call 832-325-7288. That's 832-325-7288. If you found this podcast helpful, please share it on your social channels and be sure to check out the entire podcast library for topics of interest to you. This has been Advance, the podcast series from Memorial Hermann. I'm Caitlyn Whyte. Stay well.