Non-interventional Study of Therapy for Threatened Miscarriage

Sponsor

Besins Healthcare (Industry)

Overall Status

Completed

CT.gov ID

NCT03309735

Collaborator

Clinical Research Laboratory, CRO, Russia (Other)

1,241

Enrollment

Locations

2.2

Actual Duration (Months)

Patients Per Site

33.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study the efficacy and safety of therapy for threatened miscarriage with medicinal products Utrogestan (micronized progesterone), 200 mg capsules (Besins Healthcare SA, Belgium), and Duphaston (Dydrogesterone), 10 mg coated tablets (Abbott Healthcare Products B.V., the Netherlands)

Condition or Disease	Intervention/Treatment	Phase
Threatened Miscarriage	Drug: Micronized progesterone Drug: Micronized progesterone Drug: Dydrogesterone

Detailed Description

Open comparative non-interventional study.

During the study three visits are planned:

Visit 1 (enrollment) is conducted when the patient is hospitalized in a hospital (providing medical care to pregnant women diagnosed with threatened miscarriage) due to the threat of miscarriage when the inclusion/exclusion criteria are met (women aged 18-35 years with a confirmed threat of miscarriage with a gestation period of 8 to 22 full weeks). Depending on the chosen therapy tactics (this therapy is routine in Russia), all patients are allocated to one of the three study groups:

Group I receives Utrogestan (micronized progesterone), 200 mg orally thrice a day until acute symptoms of the threat of termination of pregnancy (scarlet discharge from the genital tract, pain in the abdomen) and then Utrogestan vaginally 200 mg twice a day and 200 mg orally once a day before bed; Group II receives Utrogestan (micronized progesterone) vaginally 200 mg twice a day and 200 mg orally once a day before bed; Group III receives Duphaston (Dydrogesterone), orally 40 mg once, then 10 mg every 8 hours until the symptoms disappear.

Visit 2 (on the third day of the study/hospitalization). If pregnancy is interrupted earlier, Visit 3 is made.

Visit 3 (on the day of discharge from the hospital: with prolonged or interrupted pregnancy)

Routine clinical procedures (accepted in Russia) will be performed during the study:

Collection of demographic and anthropometric data (age, height, body weight);
Collection of complaints, medical and obstetric-gynecological history;
Measurement of blood pressure, heart rate, respiratory rate and body temperature;
Gynecological examination with the help of gynecological specula;
Vaginal bimanual examination;
Transvaginal ultrasound, determination of viability of uterine pregnancy (determination of embryo/fetal heartbeat);
Assessment of the severity of the patient's condition according to Clinical Global Impression scale;
Evaluation of psycho-emotional status dynamically using Zigmond-Snaith Hospital Anxiety and Depression Scale;

Efficacy will be evaluated using primary and secondary efficacy endpoints.

Primary efficacy endpoint:

• Discharge from the hospital with prolonged pregnancy;

Secondary efficacy endpoint:

Speed of arrest of symptoms of threatened miscarriage (blood discharge from the genital tract and drawing pains in the lower abdomen);
Duration of hospitalization;
Severity of patient's condition dynamically in the course of therapy;
Psycho-emotional status of women dynamically in the course of therapy;

Criteria for safety evaluation:

• Evaluation of AE/SAE. All adverse events (As) and serious adverse events (SAE) will be recorded, starting from the moment of signing of informed consent before the end of participation in the study (before discharge from the hospital).

Study Design

Study Type:

Observational

Actual Enrollment :

1241 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Multicenter Open Prospective Comparative Non-interventional Study of Therapy for Threatened Miscarriage With Medicinal Products Utrogestan, 200 mg Capsules (Besins Healthcare SA, Belgium), and Duphaston, 10 mg Coated Tablets (Abbott Healthcare Products B.V., the Netherlands)

Actual Study Start Date :

Oct 16, 2017

Actual Primary Completion Date :

Dec 22, 2017

Actual Study Completion Date :

Dec 22, 2017

Arms and Interventions

Arm	Intervention/Treatment
1 Utrogestan, 200 mg orally thrice a day until acute symptoms of the threat of termination of pregnancy (scarlet discharge from the genital tract, pain in the abdomen) and then Utrogestan vaginally 200 mg twice a day and 200 mg orally once a day before bed	Drug: Micronized progesterone Utrogestan, 200 mg orally thrice a day until acute symptoms of the threat of termination of pregnancy (scarlet discharge from the genital tract, pain in the abdomen) and then Utrogestan vaginally 200 mg twice a day and 200 mg orally once a day before bed Other Names: Utrogestan
2 Utrogestan vaginally 200 mg twice a day and 200 mg orally once a day before bed	Drug: Micronized progesterone Utrogestan vaginally 200 mg twice a day and 200 mg orally once a day before bed Other Names: Utrogestan
3 Duphaston, orally 40 mg once, then 10 mg every 8 hours until the symptoms disappear	Drug: Dydrogesterone Duphaston, orally 40 mg once, then 10 mg every 8 hours until the symptoms disappear Other Names: Duphaston

Arm

Intervention/Treatment

Utrogestan, 200 mg orally thrice a day until acute symptoms of the threat of termination of pregnancy (scarlet discharge from the genital tract, pain in the abdomen) and then Utrogestan vaginally 200 mg twice a day and 200 mg orally once a day before bed

Drug: Micronized progesterone

Other Names:

Utrogestan

Utrogestan vaginally 200 mg twice a day and 200 mg orally once a day before bed

Drug: Micronized progesterone

Utrogestan vaginally 200 mg twice a day and 200 mg orally once a day before bed

Other Names:

Utrogestan

Duphaston, orally 40 mg once, then 10 mg every 8 hours until the symptoms disappear

Drug: Dydrogesterone

Duphaston, orally 40 mg once, then 10 mg every 8 hours until the symptoms disappear

Other Names:

Duphaston

Outcome Measures

Primary Outcome Measures

Prolongation of pregnancy [Through study completion (until the date of patient discharge from hospital, an averade 7-14 days)]
Discharge from the hospital with prolonged pregnancy

Secondary Outcome Measures

Speed of arrest of acute symptoms of threatened miscarriage [Through study completion (until the date of patient discharge from hospital, an averade 7-14 days)]
Speed of arrest of symptoms of threatened miscarriage (blood discharge from the genital tract and drawing pains in the lower abdomen)
Duration of hospitalization [Through study completion (until the date of patient discharge from hospital, an averade 7-14 days)]
Duration of hospitalization
Severity of patient's condition [Through study completion (until the date of patient discharge from hospital, an averade 7-14 days)]
Severity of patient's condition dynamically in the course of therapy
Psycho-emotional status of patients [Through study completion (until the date of patient discharge from hospital, an averade 7-14 days)]
Psycho-emotional status of women dynamically in the course of therapy

Other Outcome Measures

Evaluation of AE/SAE [From the moment of signing of informed consent through study completion (until the date of patient discharge from hospital, an averade 7-14 days)]
All adverse events (AE) and serious adverse events (SAE) will be recorded during the study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent of the patient to participate in the study;
Women aged 18-35 years;
Progressive uterine pregnancy at the time of inclusion in the study from 8 to 22 full weeks;
Drawing pains in the lower abdomen, lumbar region;
Scanty blood discharge from the genital tract;
Palpitation of the fetus revealed by ultrasound;
Prescription by attending physician of Utrogestan or Duphaston, depending on chosen treatment tactics.

A physician should decide on the therapy, as well as tactics of further management of pregnancy before the patient is enrolled in the study and regardless of it.

Exclusion Criteria:

Stimulated ovulation, use of assisted reproductive technologies;
Abnormalities in the structure of the uterus;
Amputation of the cervix;
Uterine myoma with submucosal location of the node (a clinically significant size);
Karyotype anomalies of parents (if applicable);
Aneuploidy, anembrion, fetal malformations, as established causes of loss of previous pregnancies;
Congenital thrombophilia: factor V gene mutation (Leiden mutation), mutation of the prothrombin gene (if applicable);
Non-developing pregnancy;
Other clinically significant causes of miscarriage identified during examination (including but not limited to): pre-pregnancy diabetes, pre-pregnancy uncompensated thyroid dysfunction, history of malignant tumors or current tumors, psychiatric illnesses;
STDs at the time of inclusion in the study;
Administration of enzyme-inducing medicinal products (anticonvulsants, antipsychotics, antidepressants, tranquilizers), use of psychoactive substances before and during pregnancy;
Multiple pregnancy;
Patients previously included in this study, but who withdrew from the study for any reason;
Contraindications to therapy with Utrogestan and Duphaston, listed in approved prescribing instructions;
Contraindications to pregnancy prolongation;
Any other clinical conditions that, as seen by investigator, contradict inclusion criteria, may lead to the early termination of the patient's participation in the study or make it difficult to interpret the results of the latter;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City Clinical Hospital of the Demsk District	Ufa	Bashkortostan Republic	Russian Federation	450000
2	Maternity hospital №1	Krasnoyarsk	Krasnoyarsk Region	Russian Federation	660000
3	Regional perinatal center	Kursk	Kursk Region	Russian Federation	305000
4	Chekhov district hospital №1	Chekhov	Moscow Region	Russian Federation	142300
5	Central district hospital	Zhukovsky	Moscow Region	Russian Federation	140180
6	Center for Family Planning and Reproduction	Novosibirsk	Novosibirsk Region	Russian Federation	630000
7	Maternity hospital №2	Omsk	Omsk Region	Russian Federation	644000
8	Maternity hospital №6	Omsk	Omsk Region	Russian Federation	644000
9	City Clinical Hospital №16	Kazan	Republic Of Tatarstan	Russian Federation	420000
10	Сity hospital №7	Samara	Samara Region	Russian Federation	443000
11	Stavropol Central District Hospital	Stavropol	Stavropol Region	Russian Federation	445004
12	Сentral city hospital	Kamensk-Uralsky	Sverdlovsk Region	Russian Federation	623400
13	City Clinical Hospital № 8	Voronezh	Voronezh Region	Russian Federation	394000
14	Regional Perinatal Center	Yaroslavl	Yaroslavl Region	Russian Federation	150042
15	City Clinical Hospital №68	Moscow		Russian Federation	109263
16	Pirogov Russian National Research Medical University (RNRMU)	Moscow		Russian Federation	117997
17	Maternity hospital №17	Moscow		Russian Federation	127247