Evaluating progestogens for prevention of preterm birth international collaborative (EPPPIC) individual participant data (IPD) meta-analysis: protocol

Lesley A. Stewart; Mark Simmonds; Lelia Duley; Kristina Charlotte Dietz; Melissa Harden; Alex Hodkinson; Alexis Llewellyn; Sahar Sharif; Ruth Walker; Kath Wright

doi:10.1186/s13643-017-0600-x

Systematic Reviews

Table 1 Provisional list of trials potentially eligible for inclusion in EPPPIC (progestogen versus placebo/usual care). This table will be updated as new trials are identified. Publication details for individual trials are available on request

From: Evaluating progestogens for prevention of preterm birth international collaborative (EPPPIC) individual participant data (IPD) meta-analysis: protocol

EPPPIC identifier	Trial setting	Recruitment years	Progestogen type, dose, intervention, period Comparator	Main indication(s) Gestation at randomization	Singleton/multiple pregnancy	N
A: Eligible trials comparing progestogen with standard care or placebo^a
1	Single center Egypt (Cairo)	2008–2009	Vaginal Micronized progesterone 400 mg suppository daily 18–24 to 37 weeks Placebo	First pregnancy by IVF/ICSI 18–24 weeks	SingletonTwin	313
2	Single center Iran (Khorramabad)	–	Vaginal Progesterone 100 mg daily 24 to 34 weeks Standard care	Previous SPTBProphylactic cerclage Uterine anomalies Gestation unclear	Singleton	150
3	Single center Lebanon (Beirut)	2006–2012	Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 36 weeks Castor oil	Twin pregnancy 12–20 weeks	Twin	293
4	Multi center USA	2004–2006	Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 35 weeks Castor oil	Triplet pregnancy 16–20 weeks	Triplet	134
5	Single center Turkey (Istanbul)	2004–2007	Vaginal Progesterone 100 mg suppository daily 24 to 34 weeks Placebo	Twin pregnancy Previous SPTB Uterine anomalies 24 weeks	Singleton Twin	160
6	Multi center USA	2004–2008	Intramuscular injection 17-OHPC 250 mg weekly 16–24 to 34 weeks Castor oil	Trichorionic-triamniotic triplet pregnancy 15–23 weeks	Triplet	81
7	Multi center USA	2004–2009	Intramuscular injection 17-OHPC 250 mg weekly 16–24 to 34 weeks Castor oil	Dichorionic-diamniotic twin pregnancy 15–23 weeks	Twin	240
8	Multi center Australia	2005–2009	Vaginal Progesterone 100 mg suppository nightly 20–24 to 34 weeks Placebo	SPTB preceding pregnancy 18–24 weeks	Singleton	787
9	Single center Brazil (São Paulo)	1996–2001	Vaginal Progesterone 100 mg suppository nightly 24 to 34 weeks Placebo	Previous SPTBPrevious cerclage Uterine anomalies Gestation not reported	Singleton	157
10	Single center Egypt (Cairo)	–	Vaginal Progesterone 200 mg daily 24 to 34 weeks Placebo	Twin pregnancy	Twin	100
11	Multi center International	2003–2006	Vaginal Progesterone 200 mg suppository nightly 24–25 to 34 weeks Safflower oil	Short cervix (≤15 mm) 20–25 weeks	Singleton twin	250
12	Single center Pilot USA (Ohio)	2006–2009	Oral Micronized progesterone 2 × 200 mg capsule daily 16–20 to 34 weeks Placebo	Previous live SPTB < 20 weeks	Singleton	^b33
13	Multi center USA	2007–2011	Intramuscular injection 17-OHPC 250 mg weekly 16–23 to 37 weeks Castor oil	Nulliparous Short cervix (< 30 mm) 16–23 weeks	Singleton	657
14	Single center Finland (Oulu)	–	Intramuscular injection 17-OHPC 250 mg weekly 28–33 to 37 weeks Placebo	Twin pregnancy 28–33 weeks	Twin	77
15	Multi center International	2008–2010	Vaginal Progesterone 90 mg gel daily 20–24 to 37 weeks Placebo	Short cervix (10–20 mm) 19–24 weeks	Singleton	465
16	Single center Egypt (Cairo)	2006–2008	Intramuscular injection 17-OHPC 250 mg weekly Second trimester to 36 weeks Saline	Previous SPTB Second trimester	Singleton	50
17	Single center USA (Baltimore)	–	Intramuscular injection 17-OHPC 250 mg weekly Unclear to 37 weeks Castor oil + benzyl benzoate	2 previous SPTB 2 SAs or (1 SPTB and 1 SA) in immediately preceding pregnancy < 24 weeks	Singleton Twin	50
18	Multi center Netherlands	2006–2009	Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 36 weeks Castor oil	Multiple pregnancy 15–19 weeks	Twin Triplet Quadruplet	671
19	Single center India (Chandigarh)	2004–2006	Vaginal Micronized progesterone 100 mg capsule nightly 20–24 to 36 weeks Standard care	Previous singleton SPTB 16–24 weeks	Singleton	100
20	Multi center USA	1999–2002	Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 36 weeks Castor oil	Previous SPTB 15–21 weeks	Singleton	463
21	Single center Albania (Tirana)	–	Intramuscular injection 17-OHPC Dose not reported, daily 15–22 to 34 weeks Oral Progesterone daily (dose not reported, daily 15–22 to 34 weeks Placebo	High risk of SPTB 15–22 weeks	–	121
22	Multi center UK	2004–2008	Vaginal Progesterone 90 mg gel daily 24 to 34 weeks Placebo	Twin pregnancy 22 weeks	Twin	500
23	Multi center UK	2009–2013	Vaginal Progesterone 200 mg suppository nightly 22–24 to 34 weeks Placebo	Previous SPTB Short cervix (≤ 25 mm) Positive FFT and other risk factors for SPTB	Singleton	1228
24	Multi center USA	2004–2007	Vaginal Progesterone 90 mg gel daily 18–23 to 37 weeks Vaginal moisturizer	Singleton SPTB in most recent pregnancy 16–23 weeks	Singleton	659
25	Single center Iran (Tehran)		Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 34 weeks Placebo	Women ≥ 35 years	–	260
26	Single center India (Delhi)	2005–2006	Oral Micronized progesterone 100 mg capsule twice daily 18–24 to 36 weeks Placebo	Previous SPTB 18–24 weeks	Singleton	150
27	Multi center Denmark and Austria	2006–2008	Vaginal Micronized progesterone 200 mg suppository daily 20–24 to 34 weeks Safflower oil, gelatine, glycerol, titanium dioxide (E171)	Diamniotic twin pregnancy Chorionicity <16 weeks 18–24 weeks	Multiple	677
28	Multi center USA	2004–2006	Intramuscular injection 17-OHPC 250 mg weekly 16–20 to 35 weeks Castor oil	Twin pregnancy 16–20 weeks	Twin	661
29	Single center Iran (Mashhad)	2007–2008	Intramuscular injection 17-OHPC 250 mg weekly 16 to 37 weeks Standard care	Previous SPTB Not reported	Singleton	100
30	Multi center France	2006–2010	Intramuscular injection 17-OHPC 500 mg twice weekly 24–32 to 36 weeks Standard care	Dichorionic diamniotic twin pregnancy Cervix ≤25 mm 24–32 weeks	Twin	165
31	Multi center Spain	2006–2008	Vaginal Progesterone (1) 2 × 200 mg suppository nightly (2) 1 × 200 mg + 1 × placebo suppository nightly 20 to 34 weeks (3) 2 x placebo suppository nighly Peanut oil + soy lecithin	Dichorionic diamniotic twin pregnancy 20 weeks	Twin	294
32	Two center Canada (Calgary)	2006–2010	Vaginal Progesterone 90 mg gel daily 16–21 to 36 weeks Placebo	Multiple gestation 16–21 weeks	Twin Triplet	84
33	Single center Brazil (São Paulo)	2007–2013	Vaginal Progesterone 200 mg suppository nightly 18–21 to 34 weeks Placebo	Naturally conceived diamniotic twin pregnancy 18–21 weeks	Twin	390
34	Single center Iran (Tehran)	2010–2012	Vaginal Progesterone 400 mg suppository nightly 16–22 to 36 weeks Placebo	Previous SPTB Cervix ≤ 28 mm + cerclage Uterine anomalies Uterine intramural myoma ≥ 7 cm 16–22 weeks	Singleton	103
35	Two center Egypt (Mansoura)	2012–2014	Vaginal Progesterone 400 mg suppository daily 20–24 to 37 weeks Standard care	Dichorionic twin pregnancy Cervix 20–25 mm 20–24 weeks	Twin	250
36	Multi center Netherlands	2009–2013	Vaginal Micronized progesterone 200 mg suppository daily 22 to 34 weeks Placebo	Nulliparous Multiparous without SPTB < 34 weeks gestation Cervix ≤30 mm 18–22 weeks	Singleton	80
37	Single center India (Shimla)	–	Vaginal Progesterone 100 mg suppository 24–28 to 34 weeks Placebo	Previous SPTB 24–28 weeks	Singleton	80
38	Single center Pakistan (Bahalwapur)	2011	Intramuscular injection 17P 250 mg weekly 16–20 to 36 weeks Placebo	Previous SPTB 16–20 weeks	Singleton	60
45	Single center USA (Jackson)	–	Intramuscular injection 17-OHCP 250mg weekly Up to 34 weeks or delivery Castor oil	Twin pregnancy 20–30 weeks	Twin	30
B: Eligible trials comparing different types of progestogen
21	Single center Albania (Tirana)	–	Intramuscular injection 17-OHPC Dose not reported, daily 15–22 to 34 weeks Oral Progesterone daily (dose Dose not reported, daily 15–22 to 34 weeks Placebo	High risk of SPTB 15–22 weeks	–	121
39	Single center Egypt (Tanta)	2010–2011	Vaginal Micronized progesterone 200 mg suppository daily 20–24 to 34 weeks Intramuscular injection Progesterone 100 mg every 3rd day 20–24 to 34 weeks	Previous SPTB Cervix ≥ 15 mm 20–24 weeks	Singleton	160
40	Single center Iran (Yazd)	2012–2015	Vaginal Progesterone 200 mg suppository daily 16–20 to delivery Intramuscular injection 17-OHPC 250 mg weekly 16–20 weeks to delivery	Previous SPTB or Cervix < 25 mm (not both) 16–20 weeks	Singleton	78
41	Single center Saudi Arabia (Khamis Mushayt)	2009–2011	Vaginal Micronized progesterone 90 mg gel daily 14–18 to 36 weeks Intramuscular injection 17-OHPC 250 mg weekly 14–18 to 36 weeks	Previous mid-trimester SPTB Previous cerclage 14–18 weeks	Singleton	518
42	Single center Iran (Tehran)	2012–2015	Vaginal Progesterone 400 mg suppository daily 16–24 to 36 weeks 17-OHPC 250 mg weekly 16–24 to 36 weeks	Cervix < 25 mm 16–24 weeks	Singleton	304
43	Single center USA (Oklahoma)	2007–2010	Intramuscular injection 17-OHPC 250 mg weekly 16–21 to 37 weeks Vaginal Micronized progesterone 100 mg suppository daily 16–21 to 37 weeks	Previous live singleton SPTB 16–21 weeks	Singleton	174
44	Single center Iran (Yazd)	2010–2011	Intramuscular injection 17-OHPC 250 mg weekly 16 to 36 weeks Placebo	Assisted conception 16 weeks	Singleton	106

^aEligibility as of 15/07/2017, eligibility of all trials subject to final confirmation. Abbreviations used: IVF/ICSI in vitro fertilization/intracytoplasmic sperm injection, N number randomized, SPTB spontaneous preterm birth, IMI intramuscular injection, SA spontaneous abortion, FFT fetal fibronectin test
^bAnalyzed, not randomized (number randomized unclear)

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