NCT03565211: SARA

Clinical Safety Study of the Progesterone Vaginal Ring in Women Undergoing Assisted Reproductive Technology Procedures

Completed Phase 3 Results posted Last updated 23 November 2020

What this trial tests

Phase 3 trial testing Progesterone vaginal ring in Progesterone Supplementation in Women Undergoing ART in 352 participants. Completed in 29 July 2019.

Timeline

26 July 2018

Primary endpoint
29 July 2019

29 July 2019

Quick facts

Lead sponsor	Ferring Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	352
Start date	26 July 2018
Primary completion	29 July 2019
Estimated completion	29 July 2019
Sites	15 locations across United States

Drugs / interventions tested

• Progesterone vaginal ring — full drug profile →

Conditions studied

• Progesterone Supplementation in Women Undergoing ART — all drugs for Progesterone Supplementation in Women Undergoing ART →

Sponsor

Ferring Pharmaceuticals — full company profile →

Who can join

Adults 18 to 34, female only, with Progesterone Supplementation in Women Undergoing ART. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cumulative Rate of Spontaneous Abortions Occurring on or Before 12 Weeks Post-oocyte Retrieval Primary · On or before 12 weeks post-oocyte retrieval

Frequency of participants with spontaneous abortions on or before 12 weeks post-oocyte retrieval and undergoing fresh embryo transfer was presented. Spontaneous abortion was defined as two positive beta-human chorionic gonadotropin (β-hCG) tests occurring at least two days apart on or after 2 weeks post-oocyte retrieval, but followed by observation of any empty intrauterine gestational sac (blighted ovum), intrauterine gestation without a fetal heart beat, or absence of viable fetuses, as documented by transvaginal ultrasound (TVUS).

Group	Value	95% CI
Progesterone Vaginal Ring	7.4	4.4 – 11.5

Cumulative Rate of Spontaneous Abortions Occurring at 6 Weeks Post-oocyte Retrieval Secondary · At 6 weeks post-oocyte retrieval

Frequency of participants with spontaneous abortions at 6 weeks post-oocyte retrieval was presented.

Group	Value	95% CI
Progesterone Vaginal Ring	5.8	3.2 – 9.5

Cumulative Rate of Spontaneous Abortions Occurring at 10 Weeks Post-oocyte Retrieval Secondary · At 10 weeks post-oocyte retrieval

Frequency of participants with spontaneous abortions at 10 weeks post-oocyte retrieval was presented.

Group	Value	95% CI
Progesterone Vaginal Ring	7.4	4.4 – 11.5

Cumulative Rate of Biochemical Abortion Within 6 Weeks Post-oocyte Retrieval Secondary · Within 6 weeks post-oocyte retrieval

Frequency of participants with biochemical abortions within 6 weeks post-oocyte retrieval was presented. Biochemical abortion was defined as a positive β-hCG test at 2 weeks and 2 weeks +3-4 days post-oocyte retrieval, but followed by no observed gestational sac on a later TVUS, or followed by a negative β-hCG test.

Group	Value	95% CI
Progesterone Vaginal Ring	10.3	6.8 – 14.8

Cumulative Rate of Biochemical Abortion Within 10 Weeks Post-oocyte Retrieval Secondary · Within 10 weeks post-oocyte retrieval

Frequency of participants with biochemical abortions within 10 weeks post-oocyte retrieval was presented.

Group	Value	95% CI
Progesterone Vaginal Ring	10.3	6.8 – 14.8

Positive β-hCG Rate at 2 Weeks and 2 Weeks +3-4 Days Post Oocyte Retrieval Secondary · At 2 weeks and 2 weeks +3-4 Days post oocyte retrieval

Frequency of participants with positive β-hCG rate at 2 weeks and 2 weeks +3-4 Days was presented. Positive β-hCG was defined as a positive serum β-hCG test at 2 weeks and 2 weeks +3-4 Days post-oocyte retrieval.

Group	Value	95% CI
Progesterone Vaginal Ring	60.9	54.5 – 67.1

Clinical Pregnancy Rate at 6 Weeks Secondary · At 6 weeks post-oocyte retrieval

Frequency of participants with clinical pregnancy at 6 weeks was presented. Clinical pregnancy was defined as a TVUS showing at least 1 intrauterine gestational sac with fetal heart-beat at 6 weeks post-oocyte retrieval.

Group	Value	95% CI
Progesterone Vaginal Ring	44.9	38.5 – 51.3

Clinical Pregnancy Rate at 10 Weeks Secondary · At 10 weeks post-oocyte retrieval

Frequency of participants with clinical pregnancy at 10 weeks was presented.

Group	Value	95% CI
Progesterone Vaginal Ring	43.2	36.9 – 49.7

Rate of Ectopic and Heterotopic Pregnancies Following Oocyte Retrieval Secondary · At 4 weeks +3-4 Days after oocyte retrieval

Frequency of participants with ectopic and heterotopic pregnancies was presented.

Ectopic pregnancy

Group	Value	95% CI
Progesterone Vaginal Ring	0.4	0.0 – 2.3

Heterotopic pregnancy

Group	Value	95% CI
Progesterone Vaginal Ring	0.0	0.0 – 1.5

Rate of Abnormal Findings in Clinical Laboratory Tests (Clinical Chemistry, Hematology, and Urinalysis) Secondary · From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)

Participants with at least one abnormal finding in clinical laboratory tests (i.e. abnormal clinical significant \[CS\] values: as assessed by investigator) were reported. Clinical chemistry included: glucose, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, potassium, sodium, chloride, calcium, estimated glomerular filtration rate, and gamma-glutamyl transferase; hematology included: basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, erythrocytes, and leukocytes; urinalysis included: specific gravity, ketones,

Potassium (mmol/L)<3.5->5.3

Group	Value	95% CI
Progesterone Vaginal Ring	1

Blood, traces

Group	Value	95% CI
Progesterone Vaginal Ring	1

Rate of Abnormal Findings in Vital Signs Secondary · From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)

Participants with at least one abnormal finding (i.e. abnormal CS values: as assessed by investigator) in vital signs were reported. Vital signs includes: Weight (kg): decrease of \>=7% from baseline (BL) or increase of \>=7% from BL; Systolic Blood Pressure (SBP): \<=90 mmHg and decrease of \>=20 mmHg from BL or \>=180 mmHg and increase of \>= 20 mmHg from BL; Diastolic Blood Pressure (DBP): \<= 50 mmHg and decrease of \>= 15 mmHg from BL or \>=105 mmHg and increase of \>=15 mmHg from BL; Heart Rate: \<=50 (beats per minute \[bpm\]) and decrease of \>= 15 bpm from BL or \>=120 bpm and increas

Weight (kg), decrease of >=7% from BL

Group	Value	95% CI
Progesterone Vaginal Ring	4

Weight (kg), increase of >=7% from BL

Group	Value	95% CI
Progesterone Vaginal Ring	23

SBP (mmHg), <=90 and decrease >=20 from BL

Group	Value	95% CI
Progesterone Vaginal Ring	2

DBP (mmHg), <=50 and decrease of>=15 from BL

Group	Value	95% CI
Progesterone Vaginal Ring	3

DBP(mmHg),>=105 and increase of>=15 from BL

Group	Value	95% CI
Progesterone Vaginal Ring	1

Heart Rate(bpm) <=50 and decrease of>= 15 from BL

Group	Value	95% CI
Progesterone Vaginal Ring	1

Heart Rate(bpm) >=120 and increase of>= 15 from BL

Group	Value	95% CI
Progesterone Vaginal Ring	1

Frequency, Intensity/Grade, Seriousness, and Relatedness of Adverse Events (AEs) Secondary · From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)

The frequency of participants with total AEs, AEs by categories of intensity (mild, moderate, severe), seriousness and relatedness was presented. An AE is any untoward medical occurrence in a participant participating in a clinical trial. The intensity of an AE was classified using the following 3-point scale: mild=awareness of signs or symptoms, but no disruption of usual activity; moderate=event sufficient to affect usual activity (disturbing); or severe= inability to work or perform usual activities (unacceptable). Seriousness refers to death, hospitalization/ prolongation of existing hospi

Any AE

Group	Value	95% CI
Progesterone Vaginal Ring	124

Mild AE

Group	Value	95% CI
Progesterone Vaginal Ring	100

Moderate AE

Group	Value	95% CI
Progesterone Vaginal Ring	46

Severe AE

Group	Value	95% CI
Progesterone Vaginal Ring	9

Serious AE

Group	Value	95% CI
Progesterone Vaginal Ring	4

ADRs

Group	Value	95% CI
Progesterone Vaginal Ring	25

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were monitored from the time of obtaining informed consent until the last visit (end of trial) (up to approximately 4.5 months) .. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Progesterone Vaginal Ring

Serious: 4/254 (2%)

Deaths: 0/254

Serious adverse events (4 terms)

Reaction	System	Progesterone Vaginal Ring
Ectopic pregnancy	Pregnancy, puerperium and perinatal conditions	—
Suicidal ideation	Psychiatric disorders	—
Adnexal torsion	Reproductive system and breast disorders	—
Ovarian cyst ruptured	Reproductive system and breast disorders	—

Other adverse events (4 terms — click to expand)

Reaction	System	Progesterone Vaginal Ring
Biochemical pregnancy	Pregnancy, puerperium and perinatal conditions	—
Nausea	Gastrointestinal disorders	—
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	—
Headache	Nervous system disorders	—

Most-reported serious reactions: Ectopic pregnancy, Suicidal ideation, Adnexal torsion, Ovarian cyst ruptured.

Data from ClinicalTrials.gov NCT03565211 adverse events section.

Sponsor's own description

The purpose of the study is to assess the safety of Progesterone Vaginal Ring (PVR) in women undergoing fresh embryo transfer (ART).

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Safety evaluation of a novel progesterone vaginal ring (PVR) for luteal phase support: SARA trial.
   Stadtmauer LA, Schnell VL, Park JK, Slater CC, et al · · 2026 · PMID 42213348 · DOI 10.1007/s13346-026-02158-x