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This study aims to assess the effect of different hormonal contraceptives on 24-h blood pressure in cycling women aged 18-50 years of age.
The main question aims to answer:
- Does oral contraceptives, estrogen formulations' based combined with drospirenone or the only drospirenone present minr effect on blod pressure and/or on the heart rate?
Participants will:
Aim of this study is to investigate a possible minor effect on blood pressure and, secondarily, on heart rate of oral contraceptives based on the new estrogen formulations combined with drospirenone or with the administration of drospirenone alone.
The seecondary objectives are:
The experimental flow will have a:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ethynyl estradiol and Drospirenone | Drug | Oral ethynyl estradiol (20 mcg) and 3 mg drospirenone for 24 days and 4 days free of hormones | ||
| Drospirenone | Drug | A drospirenone (4mg) only pill | ||
| Estetrol and Drospirenone | Drug | Oral estetrol (15 mg) and drospirenone (3 mg) for 24 days and 4 days of interval free of hormone |
| Measure | Description | Time Frame |
|---|---|---|
| Rhythmometric evaluation by cosinor analysis | When cosinor analysis is significant, we calculate and record the nadir (time of minimal cosine function; that is, the time in the 24-h period when mean BP and heart rate are at their theoretical minimum). Rhythms are put in phase by considering the nadir as the circadian time 0. The 24-h, daytime, and night-time (3 h before and 3 h after the time of nadir) values are separately evaluated. Assuming a difference in blood pressure o heart rate of 3 mmHg with a standard deviation of the difference of 6 mmHg and setting type I error at 0.05 and type II error at 0.20, 32 women need to be enrolled in each group of treatment. | From starting of the treatment to the end of it at 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of modifications induced by treatments | From starting of the treatment to the end of it at 4 months | |
| Identification of the parameters conditioning the eventual BP or heart rate response to treatments | From starting of the treatment to the end of it at 4 months |
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Inclusion Criteria:
Exclusion Criteria:
Contraindications for contraceptive steroids:
Presence or a history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident;
Precence or history of prodromi of a thrombosis (e.g. transient ischaemic attack, angina pectoris);
History of migraine with focal neurological symptoms;
Diabetes mellitus with vascular involvement;
The presence of a severe or multiple risck factor(s) for venous or arterial thrombosis (to be judged by the (sub)-investigator).
e.g. increasing age; smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age); a positive family history (i.e. venous or arterial thromboembolism ever in a sibling or parent at an age< 40 years o); obesity (body mass index over 30 kg/m2); dyslipoproteinaemia; hypertension, migraine, valvular heart disease, atrial fibrillation; prolonged immobilization, major surgery any surgery to the legs, or major trauma (until two weeks after full remobilization); systemic lupus erythematosus; haemolytic uraemic syndrome; chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis); sickle cell disease;
Severe dyslipoproteinemia
Blood pressure above 140/90 mmHg
Known hereditary or acquired predisposition for venous or arterial thrombosis, such as APC resistance, antithrombin-lll-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
Pancreatitis or a history thereof if associated with severe hypertriglyceridaemia;
Presence or history of severe hepatic disease as long as liver function values have not returned to normal;
Presence or history of liver tumors (benign or malignant);
Known or suspected sex steroid-influenced malignancies (e.g. of the genital organs or the breasts);
Undiagnosed vaginal bleeding
Known or suspected pregnancy
Hypersensitivity to the active substances or to any of the excipients of the investigational product
An abnormal cervical smear (i.e.: dysplasia, cervical intraepithelial neoplasia (CIN), SIL, carcinoma in situ, invasive carcinoma) at the screening evaluation
Clinically relevant abnormal laboratory data as judged by the investigator;
Post-partum (6 months from delivery)
Breastfeeding or 2 months from breastfeeding ending
Present use or use in the last 2 months of the following drugs: phenytoin, barbiturates, primidone, carbamazapine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole, sex steroids (other than pre- and post-treatment contraceptive method) and herbal remedies containing Hipericum perforatum (St John's Wort);
Administration of any other investigational drugs and/or participation in other clinical trial in the last 2 months.
Present use of any oral contraceptive.
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Subjects will be recruited from outpatient hospital centre for contraception at the University Hospital San Martino of Genova (Italy). Subjects can only be included in the trial if all inclusion criteria are fulfilled, while none of the exclusion criteria are present.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Angelo Cagnacci | Contact | +39 3479715607 | angelo.cagnacci@unige.it |
| Name | Affiliation | Role |
|---|---|---|
| Angelo Cagnacci, MD, PhD | Clinica Ostetrica e Ginecologica, IRCCS-Ospedale San Martino di Genova | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ospedale San Martino | Recruiting | Genova | GE | 16132 | Italy |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D004997 | Ethinyl Estradiol |
| C035144 | drospirenone |
| C000718213 | drospirenone and estetrol |
| ID | Term |
|---|---|
| D009651 | Norpregnatrienes |
| D009650 | Norpregnanes |
| D009654 | Norsteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D042782 | Estrogenic Steroids, Alkylated |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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