Hemocoagulation and Lipoperoxidation in Women Using Combined Oral Contraceptives, Correction by Antioxidants

Sponsor

Tyumen State Medical Academy (Other)

Overall Status

Unknown status

CT.gov ID

NCT02027337

Collaborator

(none)

200

Enrollment

Location

Arms

Duration (Months)

9.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

We investigate parameters of hemocoagulation and lipoperoxidation in women using combined oral contraceptives with antiandrogenic activity (containing drospirenone with 20 or 30 mcg ethinylestradiol; or cyproterone acetate); correction of these changes by antioxidants

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovarian Syndrome Hyperandrogenism Menstrual Irregularities	Drug: 20 mcg ethinylestradiol /3 mg drospirenone Drug: 20 mcg ethinylestradiol/3 mg drospirenone and Selmevit Drug: 30 mcg ethinylestradiol/3 mg drospirenone Drug: 30 mcg ethinylestradiol/3 mg drospirenone and Selmevit Drug: 35 mcg ethinylestradiol/2 mg cyproterone Drug: 35 mcg ethinylestradiol/2 mg cyproterone and Selmevit	Phase 4

Detailed Description

It is well known that hormonal contraceptives using increase risk of thrombosis. We conduct parameters of hemostasis in women that use combined oral contraceptives with antiandrogenic activity for contraception and treatment. Considering relationship between lipoperoxidation in platelets and hemostasis we expect that limitation of lipoperoxidation by antioxidants can restrict hypercoagulation and decrease risk of thrombosis.

The purpose of this study is decrease of thrombosis risk in women that use combined oral contraceptives containing 20 mcg ethinylestradiol/3 mg drospirenone, 30 mcg ethinylestradiol/3 mg drospirenone, 35 mcg ethinylestradiol/2mg cyproterone acetate. Half of the women of each arm (group) receive only combined oral contraceptives (COC), other women receive combined oral contraceptives and antioxidant complex Selmevit.

The blood tests conduct on 19-21 days of the menstrual cycle before COC use (control group) or on 19-21 days of COC use after 1, 3, 6 and 12 cycles.

Also we investigate subjective tolerability, therapeutic effects, menstrual cycle control and adverse effects of COCs in women that have or have no antioxidant complex Selmevit

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

The Changes of Hemocoagulation and Lipoperoxidation in Women Using Combined Oral Contraceptives With Antiandrogenic Activity, Correction by Antioxidants

Study Start Date :

Dec 1, 2013

Anticipated Primary Completion Date :

Mar 1, 2015

Anticipated Study Completion Date :

Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control group Healthy women that no use combined oral contraceptives
Experimental: 20 mcg EE/3 mg drospirenone Women that use combined oral contraceptives containing 20 mcg ethinylestradiol/3 mg drospirenone (Yaz)	Drug: 20 mcg ethinylestradiol /3 mg drospirenone One contraceptive pill in each day of 28 day cycle. Number of Cycles: 12 Other Names: Yaz
Experimental: 20 mcg EE/3 mg drospirenone and Selmevit Women that use combined oral contraceptives containing 20 mcg ethinylestradiol/3 mg drospirenone (Yaz) and antioxidant complex Selmevit	Drug: 20 mcg ethinylestradiol/3 mg drospirenone and Selmevit One contraceptive pill in each day of 28 day cycle. Number of Cycles: 12. Two pills of Selmevit in each day during 30 days, repeat of the course every 3 months. Other Names: Yaz Selmevit
Experimental: 30 mcg EE/3 mg drospirenone Women that use combined oral contraceptives containing 30 mcg ethinylestradiol/3 mg drospirenone (Yasmin)	Drug: 30 mcg ethinylestradiol/3 mg drospirenone One contraceptive pill in each of 21 days, than 7 days break. Number of Cycles: 12 Other Names: Yasmin
Experimental: 30 mcg EE/3 mg drospirenone and Selmevit Women that use combined oral contraceptives containing 30 mcg ethinylestradiol/3 mg drospirenone (Yasmin) and antioxidant complex Selmevit	Drug: 30 mcg ethinylestradiol/3 mg drospirenone and Selmevit One contraceptive pill in each of 21 days, than 7 days break. Number of Cycles: 12 Two pills of Selmevit in each day during 30 days, repeat of the course every 3 months. Other Names: Yasmin Selmevit
Experimental: 35 mcg EE/2mg cyproterone Women that use combined oral contraceptives containing 35 mcg ethinylestradiol/2 mg cyproterone	Drug: 35 mcg ethinylestradiol/2 mg cyproterone 1 contraceptive pill in each day of 28 day cycle. Number of Cycles: 12 Other Names: Diane-35 Chloe
Experimental: 35 mcg EE/2 mg cyproterone and Selmevit Women that use combined oral contraceptives containing 20 mcg ethinylestradiol/2 mg cyproterone and Selmevit	Drug: 35 mcg ethinylestradiol/2 mg cyproterone and Selmevit One contraceptive pill in each day of 28 day cycle. Number of Cycles: 12. Two pills of Selmevit in each day during 30 days, repeat of the course every 3 months. Other Names: Diane-35 Chloe Selmevit

Outcome Measures

Primary Outcome Measures

Change from Baseline in Activated recalcification time [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Activated partial thromboplastin time [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Prothrombin time [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in International normalized ratio [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in D-dimer concentration [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Fibrinogen concentration [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Soluble fibrin-monomer complexes concentration [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Platelet aggregation [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Antithrombin III activity [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Reserve plasminogen index [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Erythrocyte Lipoperoxidation products, extractable in heptane and isopropanol [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Malondialdehyde Concentration in Erythrocytes [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Glutathion-S-transferase Activity in Erythrocytes [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Change from Baseline in Superoxide dismutase Activity in Erythrocytes [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]
Vitamin A and E plasma concentration [Baseline, 1, 3, 6 and 12 cycles of 4 weeks (between days 18 and 21 of each cycle)]

Secondary Outcome Measures

Frequency of adverse effects [12 cycles of 4 weeks]
Subjective tolerability of contraceptives [12 cycles of 4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Women aged 18-35 years
Absence of contraindications for COC use
Informed voluntary consent for examination

Exclusion Criteria:

Age younger than 18 and older than 35 years
Refusal or failure to comply with the study protocol
Drug or alcohol dependence
Psychiatric diseases
Severe somatic and allergic diseases
Pregnancy
Malignancies
Taking drugs that affect haemostasis, including hormonal contraceptives during 6 months before study beginning
Cases of thrombosis among first-line relatives in family history
Contraindications to the COC use under Eligibility Criteria of hormonal contraception (WHO, 2012)