In 2008, Beth Frazer was almost 20 weeks into what she thought was a healthy first pregnancy when a routine doctor’s visit detected a problem that sent her to the hospital, cost the lives of the twins she carried and almost took her life.
Frazer, who lives in Nashville, was diagnosed with preeclampsia, a complication of pregnancy characterized by high blood pressure that can lead to organ failure, seizures, stroke or death of the mother and baby. Its cause is not known, and there is no cure. Treatment options are few, except in-hospital monitoring and early delivery, which could carry dire consequences for the baby.
Dr. Garrett Lam, MD, FACOG, associate professor and chair of the Department of Obstetrics and Gynecology at the University of Tennessee Health Science Center College of Medicine in Chattanooga, is hoping a clinical study he is helping to direct will change the outcome for women like Frazer in the future.
Dr. Lam is the principal investigator for the Tennessee site of the PRESERVE-1 Study, which is assessing whether administering an antithrombin (anti-clotting) drug called ATryn to women diagnosed with preeclampsia between 23 and 30 weeks of pregnancy will slow the progression of the disease. The goal is to see if the drug will significantly prolong gestation, thus improving fetal survival and long-term prospects without risking maternal safety.
Preeclampsia can occur at any point in pregnancy, most often in the later stages when babies are viable at delivery. When early onset preeclampsia — less than 32 weeks — necessitates premature delivery, babies may be too underdeveloped to survive. If babies do survive, they may have long-term problems that will affect their quality of life.
The PRESERVE-1 Study is funded by rEVO Biologics, Inc., the maker of ATryn, a man-made version of a naturally occurring protein in human blood that prevents clotting. ATryn has been approved by the FDA for prevention of blood clots in pregnant women and surgical patients unable to produce enough anti-clotting material on their own. Short-term use of antithrombin has been previously shown in two studies to prolong gestation. This is the first study looking at whether continuously infused antithrombin will have a positive effect on gestation.
The study aims to enroll 120 women with early onset preeclampsia at 20 sites across the country, including at Baroness Erlanger Medical Center in Chattanooga. An additional 10 sites are expected to be added in the future.
“Preeclampsia is the second-highest cause for maternal death worldwide,” Dr. Lam said. Though no cause has been identified, it is believed that abnormalities related to the placenta, either in formation or implantation, may set up an inflammatory reaction in the mother, triggering the syndrome. Women diagnosed with preeclampsia are known to have antithrombin levels that are lower than levels seen in women who are not pregnant. This study aims to restore a woman’s antithrombin levels to what is expected when not pregnant.
Women diagnosed with preeclampsia at 23 to 30 weeks of pregnancy are eligible for the study. They will be monitored in the hospital until they deliver, as is the current protocol for all patients with early onset of the disease. Half of the women will receive intravenous placebo treatment (an inactive saline solution), and half will receive an infusion of ATryn every day. All participants will otherwise be treated the same with close clinical observation and management, potentially including medication to lower blood pressure.
“The idea is that a consistent flooding of the body with a low dose of this medication will short circuit the inflammation process, giving the baby more time to develop and holding off the disease progression,” Dr. Lam said. “Unfortunately, the disease process will keep building, and eventually we won’t be able to hold it off. At that point, we will have to deliver. The delay could be days, a week, or longer, but every one day the mother can safely stay pregnant gives mother and baby better odds.”
Investigators are prepared to help women who qualify for PRESERVE-1 get to the nearest study site, he said.
Frazer, now the mother of two and a volunteer with the Preeclampsia Foundation, is happy to hear that the study may make pregnancy safer for women in the future. “People are finally giving preeclampsia its due,” she said. “It is one of the oldest conditions on record, and we have no known cause and no cure. Women in modern America are still dying in childbirth, and it’s really exciting that doctors and companies are showing increased interest and getting aggressive in their efforts against it.”
For more information about the PRESERVE-1 Study, go to http://preserve-1.org/.