Key Insights
- UAB has been awarded funding for GLOBal PPCM, the largest global study for peripartum cardiomyopathy. The trial will test whether a widely available drug can save the lives of women with this condition.
- The UAB Mary Heersink Institute for Global Health and Center for Research in Women’s Health are coordinating a new international trial, to test whether bromocriptine can save the lives of mothers with peripartum cardiomyopathy.
- Peripartum cardiomyopathy is a rare, life-threatening form of heart failure that develops toward the end of pregnancy or within the first five months postpartum.
- The trial will launch in 15 countries, including 13 low- and middle-income countries, at more than 15 sites and with three partner institutions.
Alan Tita, M.D., Ph.D (left) and Rachel Sinkey, M.D. (right)A new international trial, coordinated through the University of Alabama at Birmingham Mary Heersink Institute for Global Health and the Center for Research in Women’s Health, will test whether a widely available drug can save the lives of mothers with peripartum cardiomyopathy — a rare, life-threatening form of heart failure that develops toward the end of pregnancy or within the first five months postpartum.
The National Heart, Lung, and Blood Institute has awarded funding over seven years for the GLOBal PPCM trial, also known as the GLOBal trial of Bromocriptine for PeriPartum CardioMyopathy, establishing the largest and most diverse global research network addressing this disease.
The trial’s Clinical Coordinating Center at UAB is co-led by Alan Tita, M.D., Ph.D., professor in the Department of Obstetrics and Gynecology, senior associate dean for Global and Women’s Health, and director of the Mary Heersink Institute for Global Health, and Rachel Sinkey, M.D., associate professor in the Division of Maternal-Fetal Medicine. Tita and Sinkey will serve as the trial’s principal investigators and the UAB DATA Coordinating and Collaborative Research Unit will serve as the study’s Data Coordinating Center.
The DCC is funded by a separate award and will be led by principal investigator Jeff Szychowski, Ph.D., professor and chair of the Department of Biostatistics in the School of Public Health and acting director of the DATA CRU at UAB.
“Maternal health is one of the defining challenges and opportunities of global public health,” said Anupam Agarwal, M.D., senior vice president for Medicine and dean of the UAB Marnix E. Heersink School of Medicine. “This remarkable award reflects the power of collaboration and leadership by UAB investigators and their partners across the world. The GLOBal PPCM trial has the potential to improve and save the lives of women and infants across the world.”
A global network taking shape
As the largest global study of PPCM, the trial has been approved to launch in 15 countries at more than 15 sites and with three partner institutions. Additional countries and sites have the potential to join as the trial progresses.
The participating countries include:
- Bangladesh
- Cameroon
- The Democratic Republic of the Congo
- Dominican Republic
- Ethiopia
- Ghana
- Jamaica
- Kenya
- Mozambique
- Rwanda
- Uganda
- Zambia
RTI International, the University of Pittsburgh and McMaster University round out the trial’s partner institutions, contributing expertise in global trial implementation, regulatory oversight and cardiovascular clinical trials methodology.
UAB has been awarded funding for GLOBal PPCM, the largest global study for peripartum cardiomyopathy. The trial will test whether a widely available drug can save the lives of women with this condition.
For the Mary Heersink Institute for Global Health, the award’s significance extends well beyond the science it will produce. With coordinating centers anchored at UAB and investigators and teams spanning Africa, Asia, the Caribbean, Europe and North America, the trial gives the institute a durable, ready-made network of collaborative research relationships — one that can be leveraged to support future large studies in maternal and global cardiovascular health and other global priorities long after GLOBal PPCM concludes.
The health problem at the heart of the trial
Peripartum cardiomyopathy is a leading contributor to late postpartum maternal death in the United States and globally, and it disproportionately affects populations that already carry the highest burden of maternal mortality. In some low- and middle-income countries, PPCM leads to severe heart failure or death in 20 percent or more of cases. The cause of PPCM is not fully understood; but emerging evidence points to a role for prolactin, the hormone that primarily triggers breast tissue to produce milk, in the disease’s progression.
Bromocriptine, a drug that activates dopamine receptors and suppresses prolactin production, has shown promise in smaller preclinical and clinical studies for improving heart-muscle recovery and reducing maternal death and complications. What has been missing is a study large enough and global enough to know for certain whether it works and whether it is safe for both mother and infant.
A trial designed to deliver answers
GLOBal PPCM will enroll approximately 650 women with PPCM in a pragmatic, placebo-controlled trial. Researchers will test whether bromocriptine, added to standard heart failure therapy, reduces maternal death, persistent heart failure and related complications — while also closely tracking safety for both mothers and their infants, including the effects of potential bromocriptine-induced lactation suppression, an important consideration in breastfeeding populations.
“Peripartum cardiomyopathy remains one of the most devastating complications of pregnancy, particularly in the U.S. and other settings where maternal mortality remains high,” Tita said. “This trial represents years of planning and collaborative partnership across continents to answer a question that has enormous implications for mothers and families around the world.”
Tita also notes that the goal is to generate definitive evidence that can immediately inform clinical practice and save lives.
The question of whether a promising but unproven therapy can change outcomes is exactly what the trial and its leaders set out to answer.
“Bromocriptine has shown encouraging signals in smaller studies; but the field has lacked the large-scale evidence needed to determine whether it improves the outcomes that matter most, including survival and serious maternal morbidity,” Sinkey said. “GLOBal PPCM was specifically designed to address that gap while also rigorously evaluating maternal and infant safety.”
The trial builds on existing international research collaborations, including centers affiliated with the National Institute of Child Health and Human Development Global Network, and reflects years of consultation with NHLBI leadership, investigators, ethics experts and community advisory boards across participating countries.
“We are thrilled that the NICHD Global Network can play such a pivotal role in the launch of GLOBal PPCM. It is well known that PPCM can gravely affect the mother; but this trial will also evaluate potential benefits of treatment that may extend to their infants, who are often affected when their mother is critically ill,” said Wally Carlo, M.D., UAB Division of Neonatology director and the U.S. principal investigator for the Zambia NICHD Global Network site, in partnership with Zambia lead Elwyn Chomba, M.D.
If successful, GLOBal PPCM could change how mothers with this disease are treated everywhere and open the door to deeper research into how to protect women’s heart health long after they have brought new life into the world.
“This is a remarkable achievement for Dr. Tita and the entire GLOBal PPCM team,” said Ashley Battarbee, M.D., associate professor in the Division of Maternal-Fetal Medicine and director of the Center for Research in Women’s Health. “This trial reflects years of hard work and the strength of UAB’s collaborative research enterprise, from the Mary Heersink Institute for Global Health to the NICHD Global Network, to the infrastructure CRWH provides for women’s health research.”