Years of research in to how to best help babies struggling to grow in the womb has culminated in the world’s first clinical trial treating at-risk pregnant mothers with sildenafil citrate (the generic of a better known brand, Viagra), right here in New Zealand.
The first in an international collaborative network of trials, the New Zealand STRIDER trial will test the treatment in a trial of eligible pregnant women carrying babies suffering from severe intrauterine growth restriction (IUGR) using sildenafil or an identical placebo tablet, administered under close clinical obstetric care.
Sildenafil citrate is best known for its effects on the blood supply of the male pelvis. However fifteen years ago, Professor Phil Baker (Director of Gravida: National Centre for Growth and Development), began testing the idea that it could have a similar effect on pregnant women – and increase blood flow to the womb and developing baby. Using human tissue samples and animal studies, Professor Baker and other research groups around the world have since provided evidence that sildenafil may increase the growth rates of very small babies in the womb and help them to be born safely at a later gestation and at a healthier, larger size.
Sadly, without intervention, many of these severely growth-restricted pregnancies end in stillbirth or extremely pre-term delivery - sometimes resulting in severe, life-threatening conditions and conditions such as cerebral palsy, blindness or brain injuries. Many families suffer extreme stress, income loss due to absence from work, and have to cope with ongoing difficulties for their child. These not only include growth rate and development issues and chronic lung disease, but an increased risk of metabolic diseases such as obesity, type 2 diabetes and heart disease later in life.
“There is currently no treatment for growth restriction other than early delivery once a baby is in danger,” says the trial’s lead, Dr Katie Groom, Department of Obstetrics and Gynaecology (The University of Auckland) and Gravida Investigator. “Being born extremely prematurely and tiny, while currently the only option to save the baby’s life, does have both short and long term health consequences and obstetricians face a daily battle to try to manage the risks.
“If we can determine a therapy that enhances fetal growth, and we can therefore delay delivery, we will improve not only these babies’ survival rates but also reduce the many complications that follow and can lead to life-long disability or disease.
“In this trial we’re testing only one particular group of pregnancies – those with very severe, early onset IUGR - but if sildenafil proves it can help, we plan to trial it in later stage cases too, where it could be of benefit for many more at-risk babies and families and have a huge societal and financial effect on our population.”
The STRIDER NZAus trial is a bi-national trial with Australia, and will be run from Auckland. Funding for the study of sildenafil in pregnancy was initially granted by Gravida in 2012 and major funding for the clinical trial was granted by the Health Research Council of New Zealand in June 2013.
The trial will form part of an international network called the STRIDER IPD collaboration, which has been set up to test the drug’s efficacy in different populations around the world throughout 2013-2017. Each trial will share and compare results across countries. Other trials are being planned in the UK/Ireland, Netherlands, Canada and the US. The New Zealand trial will be the first to start recruiting women.
News article courtesy of Gravida: National Centre for Growth and Development
Safety first, researchers stress
The New Zealand trial’s researchers caution that under no circumstances should pregnant women outside of the trial seek to take the drug.
Only mothers with extreme cases of IUGR who are under very close obstetric care, and likely to already be hospital in-patients, will be administered the drug or an identical placebo tablet by their obstetrician as part of the carefully controlled trial. Safety is a paramount concern. While sildenafil is already used in clinical practice, including in pregnant women for the management of pulmonary arterial hypertension, and in newborns suffering from pulmonary hypertension, this is the first major clinical trial of sildenafil for fetal growth.