Changes in the Use of Hydroxyprogesterone Caproate Injection After Confirmatory Trial Failure

Author(s):  
Rachel E. Sachs ◽  
Kyle A. Gavulic ◽  
Julie M. Donohue ◽  
Stacie B. Dusetzina
Author(s):  
Baha Sibai ◽  
George R. Saade ◽  
Anita F. Das ◽  
Jennifer Gudeman

Abstract 17-alpha-hydroxyprogesterone caproate (17P) has been in use for prevention of recurrent preterm birth since 2003 when the Meis trial was published. A requirement for Food and Drug Administration approval of 17P was a confirmatory trial, called “PROLONG”, which was recently completed, but did not replicate the efficacy demonstrated in the Meis trial. This review analyzes the safety data from each trial, as well as integrated data from the two trials. The relative risks (95% CI) with 17P versus placebo in the integrated dataset were 0.66 (0.25–1.78) for miscarriage, 1.83 (0.68–4.91) for stillbirth, and 0.86 (0.53–1.41) for all fetal and neonatal death. The rate of gestational diabetes in the integrated dataset was 3.6% for 17P vs. 3.8% for placebo. Similar findings with low and comparable rates between 17P and placebo were also found for other adverse events. The integrated safety data demonstrate a favorable safety profile that was comparable to placebo.


Author(s):  
Adolf E. Schindler

AbstractProgesterone appears to be the dominant hormone not only establishing a proper secretory endometrial development but also adequate decidualization to establish pregnancy and sustain pregnancy development. Progesterone is the natural immunoregulator to control the maternal immune system and not to reject the allogeneic fetus. There are two sources of progesterone: corpus luteum first and placenta later. Three progestogens can be used in pregnancy: (i) progesterone (per os, intravaginal and intramuscular), (ii) dydrogesterone (per os), and (iii) 17α-hydroxyprogesterone caproate (intramuscular). There are three indications, for which these progestogens can be clinically used either for treatment or prevention: (i) first trimester threatened and recurrent (habitual) abortion, (ii) premature labor/premature birth, and (iii) pre-eclampsia (hypertension in pregnancy). The available data are limited and only partially randomized. In threatened abortion the use of progesterone, dydrogesterone and 17α-hydroxyprogesterone caproate leads to a significant improved outcome, when at the time of threatened abortion a viable fetus has been ascertained by ultrasound. For prevention of recurrent abortion there are also some data indicating a significant effect compared with women without progestogen treatment. Prevention of preterm birth by progestogens (progesterone vaginally, orally and 17α-hydroxyprogesterone caproate intramuscularly) was significantly effective. The main study groups include pregnant women with a previous history of premature birth. However, also in women with shortened cervix use of progesterone seems to be helpful. The studies done so far in women with risk factors for pre-eclampsia or established pre-eclampsia were based on parenteral progesterone application. However, new studies are urgently needed.


2017 ◽  
Vol 216 (6) ◽  
pp. 600.e1-600.e9 ◽  
Author(s):  
David B. Nelson ◽  
Donald D. McIntire ◽  
Jeffrey McDonald ◽  
John Gard ◽  
Paula Turrichi ◽  
...  

2016 ◽  
Vol 214 (1) ◽  
pp. S9-S10
Author(s):  
Tracy A. Manuck ◽  
Scott Watkins ◽  
M. Sean Esplin ◽  
Samuel Parry ◽  
Heping Zhang ◽  
...  

2010 ◽  
Vol 65 (8) ◽  
pp. 477-478 ◽  
Author(s):  
Vincenzo Berghella ◽  
Dana Figueroa ◽  
Jeff M. Szychowski ◽  
John Owen ◽  
Gary D. V. Hankins ◽  
...  

2011 ◽  
Vol 66 (7) ◽  
pp. 393-394
Author(s):  
C. Andrew Combs ◽  
Thomas Garite ◽  
Kimberly Maurel ◽  
Anita Das ◽  
Manuel Porto

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