Trial of erectile dysfunction drug on pregnant women stopped after 11 babies die

Dutch researchers stopped a clinical trial due to the deaths of 11 babies from a lung disease after their mothers wer...

Posted: Jul 25, 2018 10:59 PM
Updated: Jul 25, 2018 10:59 PM

Dutch researchers stopped a clinical trial due to the deaths of 11 babies from a lung disease after their mothers were treated with the drug sildenafil, commonly sold as Viagra and Revatio, while pregnant, Amsterdam University Medical Center announced Monday.

The mothers were part of a clinical trial to evaluate the safety and effectiveness of the erectile dysfunction drug on unborn babies who had severe fetal growth restriction and who faced significant risk of being stillborn or dying after birth, according to a study that detailed the design and protocol of the clinical trial.

The mothers were part of a trial to evaluate the drug for unborn babies with severe fetal growth restriction

Researchers found that sildenafil was associated with a blood vessel disease in babies' lungs

Half of the 183 mothers in the trial had been treated with sildenafil while the other half were treated with a placebo. At the time they were treated, the mothers did not know which treatment they were receiving, which is standard in clinical trials.

"Fetal growth restriction happens when the growing fetus doesn't get enough nutrients or oxygen from the placenta," said neonatologist Dr. Mohan Pammi, medical director of the neonatal intensive care unit at Texas Children's Pavilion for Women in Houston, who was not involved in the Dutch study.

It sometimes occurs because the mother has high blood pressure, uncontrolled diabetes or a condition called preeclampsia, he added. And babies born too small can experience a host of problems, including smaller head sizes, lack of blood flow to the intestines and death.

The hope was that the drug "can open up some blood vessels in the placenta and then can help the growth of the fetus," Pammi said.

But the Dutch researchers found that sildenafil was associated with the babies developing a blood vessel disease in the lungs and with an increase in the risk of death after birth. The condition is essentially a type of high blood pressure in the lungs.

A similar UK trial, the results of which were published in December, found no difference in neonatal deaths, and no adverse affects were linked to the drug. But that trial also failed to show a benefit.

High blood pressure in the lungs' vessels has been linked to low birth weight, Pammi noted.

According to the statement from Amsterdam University Medical Center, 183 women had participated in the clinical trial at 11 locations in the Netherlands since it began in 2015. Ninety-three women were treated with the drug, and 90 were treated with the placebo, or dummy pill.

Nineteen babies born to the women treated with the drug died, 11 of them due to the lung disorder. Six babies were born with the lung disorder and survived. In comparison, nine babies born to women treated with the placebo died, but none of them had the lung disorder. Three babies with the lung disorder were born to women who were treated with the placebo, and they all survived.

The statement from the medical center said sildenafil is sometimes used to treat women whose babies seem to not be growing well and noted that the practice will probably be discontinued. This is in line with the conclusion by the authors of the UK study, which recommended that "clinicians worldwide should stop prescribing sildenafil for this indication outside of research studies with explicit participants' consent."

Pfizer held the drug's patent until December. Spokeswoman Dervila Keane wrote in an email Tuesday that the research is "an investigator initiated study and Pfizer have no involvement in the trial." She deferred questions to the researchers.

The company also issued a statement Wednesday noting that it did not fund or provide medication for the trial.

"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 statement said.

Low birth weight contributes to 60% to 80% of neonatal deaths worldwide, according to the World Health Organization. Its worldwide prevalence is 15.5%, comprising about 20 million children born each year, but the vast majority of low-birth-weight cases -- 96.5% -- are in developing countries.

The development of the children in the halted study will continue to be monitored and the data further analyzed, according to the medical center.

The clinical trial of sildenafil is also being conducted in the United Kingdom, Canada, and Australia and New Zealand.

Dr. Katie Groom, associate professor of maternal and perinatal health at the University of Auckland and the chief investigator of the Australia and New Zealand trial, said these lung problems and deaths were not seen there, nor in the UK, although they are reviewing all of the cases in the trial to be sure.

Dr. Ken Lim, clinical professor in the Department of Obstetrics & Gynecology at the University of British Columbia, said the trial in Canada was suspended. The trial there was started in 2017 and was still enrolling patients at three locations until it was halted after news of the deaths in the Netherlands.

"We are not aware of an increase in adverse outcomes among the 21 Canadian trial participants. We contacted the one Canadian woman who was currently in the trial, directing her to stop taking the drug or placebo. We will contact the 20 other Canadian women who have already participated in the trial," Lim wrote in an email.

Groom said the research teams in all locations will "continue to explore our data in as much detail as possible within the consortium to workout if this finding is real or chance."

She noted that the drug is used to treat pulmonary hypertension, defined by the American Heart Association as high blood pressure in the heart to lung system, so "at first review it may seem unlikely that sildenafil has caused this problem. However, it is biologically plausible that withdrawal from the drug at birth has led to a rebound effect on the pulmonary vasculature," meaning the discontinuation of the drug at birth may have led to the complication.

"Viagra is indicated for the treatment of the symptoms of erectile dysfunction in adult men (aged 18 years and over). The safety and efficacy of Viagra has been well documented in clinical studies involving more than 15,000 patients," the Pfizer statement said.

Pammi said there are sure to be questions about whether and how sildenafil may have been responsible for the deaths and pulmonary issues in the Dutch study, which may involve looking closer at the dosage the mothers received, the timing and any differences in medical care the women receive in the Netherlands versus other countries.

"Maybe they do something differently," he said.

Terre Haute
Broken Clouds
84° wxIcon
Hi: 83° Lo: 60°
Feels Like: 87°
Robinson
Scattered Clouds
80° wxIcon
Hi: 80° Lo: 58°
Feels Like: 83°
Indianapolis
Scattered Clouds
83° wxIcon
Hi: 80° Lo: 62°
Feels Like: 84°
Rockville
Scattered Clouds
76° wxIcon
Hi: 83° Lo: 59°
Feels Like: 76°
Casey
Few Clouds
84° wxIcon
Hi: 81° Lo: 60°
Feels Like: 86°
Brazil
Broken Clouds
84° wxIcon
Hi: 82° Lo: 59°
Feels Like: 87°
Marshall
Broken Clouds
84° wxIcon
Hi: 83° Lo: 59°
Feels Like: 87°
Low chance of storms tonight with clearing conditions
WTHI Planner
WTHI Temps
WTHI Radar

Latest Video

Image

Sunday Morning Forecast Update

Image

Saturday Morning Forecast Update

Image

Ryan Lieberman

Image

Zoe Stewart

Image

WVFCA Friday Night Lights

Image

Tim Hayes

Image

Keeping your house cooler without running the A.C. all day

Image

Several local groups partner to help you learn new job skills

Image

Duke Energy says scammers have a new tactic to steal your information, and it involves refund checks

Image

Richland County sees an increase in young people contracting COVID-19

WTHI Events

 

Illinois Coronavirus Cases

(Widget updates once daily at 7 p.m. CT)

Confirmed Cases: 154094

Reported Deaths: 7369
CountyConfirmedDeaths
Cook951384711
Lake10318428
DuPage9641485
Kane8078281
Will7223325
Winnebago3156105
St. Clair2265144
McHenry2248102
Kankakee141466
Unassigned1180201
Rock Island116930
Madison116770
Kendall104823
Champaign103817
Peoria64430
DeKalb63720
Boone63521
Sangamon51933
Jackson35119
McLean31515
Randolph3107
Ogle2964
Stephenson2836
LaSalle25417
Macon25022
Clinton24717
Whiteside20915
Union20519
Grundy1935
Coles19017
Iroquois1755
Tazewell1728
Knox1680
Adams1671
Monroe15513
Williamson1554
Warren1490
Cass1388
Morgan1343
Jefferson11417
Henry1111
McDonough10615
Lee1052
Vermilion892
Pulaski840
Marion770
Montgomery731
Macoupin673
Douglas610
Perry611
Jo Daviess541
Livingston542
Christian504
Jasper477
Woodford462
Franklin450
Ford421
Clark400
Jersey401
Bureau372
Menard310
Effingham301
Cumberland290
Mercer290
Johnson270
Washington250
Alexander240
Fayette243
Mason240
Moultrie240
Wabash230
Piatt210
Bond201
Carroll202
Crawford200
Hancock201
Logan200
Shelby201
Edgar190
De Witt180
Wayne181
Fulton160
Massac160
Saline160
Schuyler130
Lawrence120
Marshall120
Brown100
White100
Richland90
Greene80
Henderson80
Hamilton70
Gallatin60
Pike60
Stark60
Clay50
Edwards50
Hardin20
Calhoun10
Pope10
Putnam10
Scott10
Out of IL00

Indiana Coronavirus Cases

(Widget updates once daily at 8 p.m. ET)

Confirmed Cases: 51079

Reported Deaths: 2756
CountyConfirmedDeaths
Marion12019693
Lake5588248
Elkhart353959
Allen2939134
St. Joseph210669
Hamilton1691101
Cass16449
Hendricks1454100
Johnson1340118
Porter82638
Tippecanoe7709
Vanderburgh7276
Clark69544
Madison67464
LaPorte61628
Howard59858
Bartholomew59745
Kosciusko5754
Marshall5449
Noble51328
LaGrange4849
Boone48244
Jackson4783
Delaware47152
Hancock46736
Shelby45425
Floyd40644
Morgan34231
Monroe34028
Grant31826
Dubois3046
Henry30018
Montgomery29720
Clinton2903
White27410
Dearborn25823
Decatur25632
Lawrence25225
Vigo2528
Warrick25029
Harrison21722
Greene19432
Miami1932
Jennings17912
Putnam1738
DeKalb1694
Scott1649
Wayne1546
Daviess15017
Perry14710
Orange13723
Steuben1362
Jasper1352
Ripley1307
Franklin1278
Gibson1202
Wabash1162
Carroll1142
Fayette1067
Whitley1066
Starke1043
Newton10010
Huntington942
Jefferson862
Wells821
Randolph794
Fulton731
Knox710
Jay700
Washington681
Pulaski661
Clay645
Rush613
Posey570
Spencer541
Owen521
Benton510
Sullivan501
Adams491
Brown431
Blackford402
Fountain352
Crawford330
Switzerland320
Tipton321
Parke270
Martin260
Ohio230
Vermillion200
Warren151
Union140
Pike110
Unassigned0193