University of Alabama at Birmingham Department of Obstetrics and Gynecology and the Department of Biostatistics have been awarded a $19.31 million R01 grant by the National Institutes of Health’s Heart, Lung and Blood Institute to coordinate the most comprehensive study of chronic hypertension in pregnancy ever undertaken.The
The Chronic Hypertension and Pregnancy Project (CHAP) is a multicenter, randomized trial which will enroll between 4,700 and 5,700 pregnant women during the next six years with a primary aim to evaluate the benefits and potential harms of pharmacologic treatment of mild chronic hypertension in pregnancy, a decades-old question that has remained unanswered.
“This question has been an elephant in the room for obstetric care providers and researchers for quite some time,” said Alan Tita, M.D., Ph.D., professor of obstetrics and gynecology in UAB’s School of Medicine and principal investigator/project director for CHAP. “Everyone knows chronic hypertension causes serious and sometimes life-threatening complications for the pregnant woman and her baby, but no one really knows how best to manage the condition during pregnancy. While treatment of chronic hypertension is standard for the general population, it is uncertain whether treatment during pregnancy is beneficial or safe for the fetus. Specifically, while we know chronic hypertension adversely affects the baby’s growth, there are concerns that treatment of hypertension may also impair the baby’s growth. It’s a catch-22, and it’s one for which we need to find answers.”
Joseph Biggio, M.D., Maternal and Fetal Medicine division chief, vice chair for research and quality in Obstetrics and Gynecology, and the director of the Center for Women’s Reproductive Health, will oversee biospecimen collection for the study in an effort to uncover the underlying mechanisms for adverse outcomes. Biggio says UAB is well-positioned to conduct this expansive research effort.
“The Department of Obstetrics and Gynecology at UAB has a well-known history of successful design and performance of complex clinical trials,” Biggio said. “Our team of investigators and research personnel has considerable expertise with clinical study design and implementation at the local level, and also with the coordination of efforts across multiple sites to accomplish study recruitment and answer critically important research questions. With our experienced investigative team, we are uniquely poised to efficiently enroll patients, orchestrate the interactions with the other centers, and — at the end of the study — produce a high-quality manuscript that has the potential to change the way obstetrics is practiced.”
School of Medicine and the School of Public Health worked for almost three years with the NHLBI to plan and fine-tune a study that would help answer this question and others regarding chronic hypertension and pregnancy; it has been an issue since the late 1970s when the Hypertension Detection and Follow-up Program provided strong evidence for the benefits of treating even mild hypertension.The
“CHAP is a pragmatic trial that aims to provide a clear understanding of current practice of managing blood pressure in pregnancy compared with a more rigorous approach to the treatment of blood pressure during this period,” said Gary Cutter, Ph.D., professor of biostatistics in UAB’s School of Public Health and principal investigator of the data coordinating center for the trial. “This standard of care versus a more rigorous approach parallels the Hypertension Detection and Follow-up Program study where referred care — usual care in the community plus referral when blood pressures were found to exceed certain thresholds — was compared to a rigorous stepped-care approach to therapy.”
Chronic hypertension is the most common major medical disorder encountered during pregnancy, occurring in up to 6 percent of pregnant women in the United States. The substantial negative effect of chronic hypertension on pregnancy includes a consistent three- to five-fold increase in superimposed preeclampsia, placental abruption and adverse perinatal outcomes, including fetal or neonatal death, preterm birth, and poor fetal growth.
Chronic hypertension during pregnancy also is believed to be associated with a five- to tenfold increase in rare maternal cardiovascular and other complications, including death, stroke, pulmonary edema and acute renal failure.
Still, not treating pregnant women whose blood pressures are in the mild chronic hypertension range (less than 160/105-110 mmHg) with antihypertensive medication is the current recommendation.
|“Everyone knows chronic hypertension causes serious and sometimes life-threatening complications for the pregnant woman and her baby, but no one really knows how best to manage the condition during pregnancy."|
“In general, when the blood pressure is greater than 160 over 110, women are treated regardless of pregnancy because of concerns of stroke and other cardiovascular incidents,” Tita said. “The problem is the majority of women with chronic hypertension at the reproductive age have mild chronic hypertension. So we are talking about up to 80 percent of pregnant women with chronic hypertension who may not receive treatment, and we don’t know how that affects their pregnancy and whether that might lead to bad outcomes in the long term compared with treatment. In addition, the information that associates treatment with poor fetal growth is relatively weak, which is why we must investigate this further in a rigorous trial.”
CHAP will involve at least 16 academic clinical centers, including UAB, with approximately 30 hospitals across the United States. Columbia University, Duke University, Stanford University, University of California–San Francisco, University of Mississippi, the University of Pennsylvania, the University of Texas at Houston, the University of Texas Medical Branch in Galveston, University of Texas Southwestern, the University of Utah and Washington University in St. Louis are major partners with UAB in the project.
Managing multicenter clinical trials as the data coordinating center is a key component of being able to conduct complex clinical trials that span multiple institutions and locations, something in which the UAB School of Public Health Biostatistics group has had extensive experience.
“CHAP is one of the many trials our group manages,” Cutter said. “Our job involves developing Web-based data entry systems, quality control and quality assurance monitoring. We perform analyses for monitoring the safety and reporting of the information to external Data and Safety Monitoring Committees, which provide an outside review of the trial with the primary goal of protecting the patients. Finally, our analyses go into preparing reporting of the results along with the trial investigators.”
Jeff Szychowski, Ph.D., associate professor of public health, will help Cutter manage the data coordinating center as the deputy director.
Distinguished Professor of Medicine Suzanne Oparil, M.D., also is a co-investigator on the grant.
William W. Andrews, Ph.D., M.D., professor and chairman of Obstetrics and Gynecology will serve as CHAP steering committee chair.
The project will be implemented as a cooperative agreement with NHLBI collaborators.