Baby deaths prompt NZ researchers to review clinical trial

Researchers had wondered whether sildenafil might help babies grow by increasing blood supply to the placenta. Photo / 123RF

Overseas deaths of babies involved in a clinical trial has prompted a review from researchers who have been running an aligned study here in New Zealand.

The international research STRIDER consortium has involved four trials - one of them carried out here and in Australia - investigating a possible use for the drug sildenafil in treating fetal growth restriction.

Sildenafil is better known as the drug behind Viagra, which is used to treat male erectile dysfunction by dilating blood vessels in the pelvis.

The researchers drew on a generic version of sildenafil, not manufactured by Viagra's makers Pfizer, to investigate whether it might work the same way in pregnant women by increasing blood supply to the placenta.

But last week, one of the trials, which was being carried out in the Netherlands, was terminated early due to safety concerns.

Results from a planned interim analysis showed more babies in the sildenafil group suffered a serious lung condition, called persistent pulmonary hypertension, which may have led to 11 more liveborn babies dying before hospital discharge.

About 26.6 per cent of babies in the sildenafil group suffered a serious lung condition, compared with 5.2 per cent in the placebo group, while 26.8 per cent babies died before being discharged, compared with 14.3 per cent in the placebo group.

The Dutch trial began in 2015 and was due to run until 2020, with the participation of 350 patients.

Human trials had been given the go-ahead after successful experiments on rats.

The New Zealand and Australian study involved 122 pregnant women from New Zealand and Australia, half of whom regularly took Viagra, with the other half taking a placebo.

Its chief investigator, Associate Professor Katie Groom of the University of Auckland-based Liggins Institute, said the local study had found no evidence of a positive effect from sildenafil - but no evidence of harm.

This was consistent with the STRIDER UK findings, published in 2017.

"This finding was very unexpected and, as yet, it is unclear whether this increase in pulmonary hypertension was caused by sildenafil treatment," Groom said.

"We fully support the decision made by Dutch investigators to discontinue to the study and allow time to fully investigate the findings. Our consortium will continue to work together to achieve this."

Within the Australasian trial, only two cases of pulmonary hypertension were reported - in one case the mother had received sildenafil and the other placebo therapy.

"We had a similar number of neonatal deaths across both groups. These findings were similar in the UK trial."

Groom and her colleagues were reviewing all cases within both the UK and Australasian trials, but didn't expect this to change.

Both the UK and Australasian trials include Childhood Outcome studies, reviewing all children born to mothers who participated in the study at the age of two to three years, and these were ongoing.

In a statement, Pfizer said it was not involved in any aspect of the trial, and neither funded nor provided product for it.

"In addition, the Principle Investigators at the Amsterdam University Medical Centre have confirmed a non-Pfizer manufactured generic version of sildenafil was used but that no clinical trial participants were administered Viagra, Pfizer sildenafil or any other Pfizer medicine."

The safety and efficacy of Viagra had been well documented in clinical studies involving more than 15,000 patients, the coimpany said.

"We wish to express our sympathy for the trial participants and their families."