New clinical trial aims to save babies’ lives

New clinical trial aims to save babies’ lives with blood-flow enhancing drug treatment

Sildenafil (Viagra) may improve vascular blood supply and help babies thrive in utero

11 July 2013 - 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, Prof 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 (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.

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.

Strong body of evidence gathered over many years

Prof Baker, who is originally from the UK, will also act as one of Dr Groom’s co-investigators for the trial. He has continued to specialise in sildenafil, pre-eclampsia and growth restricted pregnancies throughout his international career. Since arriving in New Zealand in 2012, and taking up his joint positions at The University of Auckland, Liggins Institute and Gravida, he has collaborated with local researchers and clinicians to progress the research that he and others started many years ago.

Prof Baker explains that sildenafil is believed to help because of its ability to increase blood supply. In technical terms, it works by enhancing dilatation of both the maternal and fetal vascular compartments and blood vessels in the placenta, thereby increasing circulation, says Prof Baker.  By improving blood flow, the ability of oxygen and nutrients to cross the placenta increases and the baby may grow and be safely carried further towards full term.

“We are getting towards the end of what has been a very long research programme,” Prof Baker says.  “Medical breakthroughs rarely happen overnight but are the result of years of thought, effort and energy. This particular trial will run for several years, and then the results will take time to collate, quantify and publish.

“We’ve reached a point where the volume of evidence in the laboratory and animal studies is compelling and we want to translate these findings into genuine patient benefit. So across the world, different teams of investigators are working together to put together a network of trials that will fit together and provide a definitive answer.”

In addition to Dr Groom and Prof Baker, Gravida also supports a team of researchers who are investigating the potential benefits of sildenafil on both mother and baby - people like Dr Charlotte Oyston, a young trainee obstetrician.

“It’s heart-breaking to see pregnancies complicated by severe growth restriction and yet be unable to do anything about it,” Dr Oyston says.  “Sildenafil could be one of the most exciting and life changing innovations that we can offer in pregnancy care.  Gravida has given me the chance to take time away from my clinical work to discover whether we have a new therapy to offer.”

·         For more background on the history of research into sildenafil, including published paper citations, click here.

·         For more detail on the STRIDER clinical trial, click here.

·         For more information on Dr Oyston’s current research projects, and those of other Gravida researchers, click here.

ENDS

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