A randomised, double-blinded, placebo-controlled study of the phosphodiesterase type 5 inhibitor sildenafil for the treatment of preeclampsia.
OBJECTIVE
To determine if the phosphodiesterase type 5 inhibitor sildenafil prolongs pregnancy in women with preeclampsia.


METHODS
Women with preeclampsia at gestational ages 24-34 weeks were recruited from nine hospitals in the UK, and randomly assigned to sildenafil citrate or placebo. Medication was increased every 3 days from 20 mg three times daily (tid), to 40 mg, and 80 mg tid. The primary endpoint was prolongation of pregnancy from randomisation to delivery (days). Secondary endpoints were markers of maternal disease and cord pH at delivery and infant weight. Details of all adverse events were also collected. Plasma samples were taken to establish pharmacokinetic information. Data analysed on a modified intention to treat analysis. The study had a power of >95% to detect a difference of 5 days.


RESULTS
Of 35 women, 17 were allocated to sildenafil and 18 to placebo. There was no difference in time from randomisation to delivery in the two treatment groups, with a median time of 4 days (range 1-15) in the sildenafil group and 4.5 days (range 1-30) in the placebo group. Sildenafil achieved maximum drug concentrations of 48 ng/ml, 88 ng/ml, and 271 ng/ml after 3 days of 20 mg, 40 mg and 80 mg tid, respectively.


CONCLUSIONS
We have safely conducted a clinical trial of a drug not routinely used during pregnancy. Sildenafil in the escalating dose regimen 20-80 mg tid was well tolerated, with no increase in maternal or fetal morbidity or mortality but did not prolong pregnancy duration in women with preeclampsia. (ClinicalTrials.gov number, NCT 00141310).
Maternal & Fetal Health Research Centre, St Mary's Hospital, Manchester, United Kingdom. rasmith@doctors.net.uk
Rebekah A
RA
Samangaya
Gary
G
Mires
Andrew
A
Shennan
Laurence
L
Skillern
David
D
Howe
Alison
A
McLeod
Philip N
PN
Baker
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D018579:Patient Selection; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects*; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate