Continuous Postoperative Use of Low-Dose Combined Oral Contraceptivesfor for Endometriosis-Related Chronic Pelvic Pain

Sponsor

University Magna Graecia (Other)

Overall Status

Unknown status

CT.gov ID

NCT00844012

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Because ovarian sex steroids fluctuations during the menstrual cycle are implicated in the pathogenesis of the endometriosis-related chronic pelvic pain (CPP), the oral contraceptives (OCs) are used with non-contraceptive indication for this disorder.

To date, OCs are widely used as medical treatment in patients with endometriosis, in addition, they are recently experimented as post-surgical therapy. Traditional cyclic regimen, with 21 days of active pills with 7 days of placebo or suspension, is usually adopted. Furthermore, recent studies suggested that long-term continuous OCs use can be effective in the postoperative period both as second- and third- line treatments after cyclic regimen failure. In these studies a combined treatment with ethinilestradiol (0.02 mg) plus desogestrel (0.15 mg) were used and compared with baseline or ciproterone acetate.

A recent study showed a deeper ovarian and endometrial suppression with continuous OCs in comparison with cyclic OCs, providing a physiological rationale for continuous OCs use for noncontraceptive indications. Furthermore, to date, no study compared post-operative continuous versus cyclic OCs in patients with endometriosis-related CPP.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis Chronic Pelvic Pain	Drug: Continuous OC (clormadinone acetate plus ethinil-estradiol - Belara®, Grunenthal, Milan, Italy) Drug: Cyclic OC (clormadinone acetate plus ethinil-estradiol)	Phase 4

Detailed Description

Premenopausal women with endometriosis-related CPP scheduled for laparoscopic surgery to our Academic Department of Gynecology will be consecutively enrolled. Subjects with hystologically confirmed endometriosis at laparoscopy (stage I-IV of the American Society Reproductive Medicine), a subjective severity of pelvic pain by using a visual analogue scale (VAS 1-100) of at least 70, and without immediate desire of pregnancy will be enrolled.

Briefly, all patients will undergo conservative laparoscopic surgery for endometriosis. Thereafter, a low-dose monophasic OC containing 2.0 mg clormadinone acetate plus 0.03 mg ethinil-estradiol (Belara®, Grunenthal, Milan, Italy) will be administered. Patients from the experimental group will be treated with a continuous regimen, while patients from the control group will receive the OC with a cyclic regimen consisting of 21 days of active pills with 7 days of placebo. The drug and the placebo will be similar and will be labelled according to the subject number. For the overall study-period, operators and patients will be blind to the treatment allocation.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Continuous Versus Cyclic Postoperative Use of Low-Dose Combined Oral Contraceptive Belara® for the Treatment of Endometriosis-Related Chronic Pelvic Pain: a Randomized Controlled Trial.

Study Start Date :

May 1, 2009

Anticipated Primary Completion Date :

May 1, 2010

Anticipated Study Completion Date :

Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental group	Drug: Continuous OC (clormadinone acetate plus ethinil-estradiol - Belara®, Grunenthal, Milan, Italy) Low-dose monophasic OC containing 2.0 mg clormadinone acetate plus 0.03 mg ethinil-estradiol (Belara®, Grunenthal, Milan, Italy) will be administered with a continuous regimen.
Active Comparator: Control	Drug: Cyclic OC (clormadinone acetate plus ethinil-estradiol) Low-dose monophasic OC containing 2.0 mg clormadinone acetate plus 0.03 mg ethinil-estradiol (Belara®, Grunenthal, Milan, Italy) will be administered with a cyclic regimen.

Arm

Intervention/Treatment

Experimental: Experimental group

Drug: Continuous OC (clormadinone acetate plus ethinil-estradiol - Belara®, Grunenthal, Milan, Italy)

Low-dose monophasic OC containing 2.0 mg clormadinone acetate plus 0.03 mg ethinil-estradiol (Belara®, Grunenthal, Milan, Italy) will be administered with a continuous regimen.

Active Comparator: Control

Drug: Cyclic OC (clormadinone acetate plus ethinil-estradiol)

Low-dose monophasic OC containing 2.0 mg clormadinone acetate plus 0.03 mg ethinil-estradiol (Belara®, Grunenthal, Milan, Italy) will be administered with a cyclic regimen.

Outcome Measures

Primary Outcome Measures

Recurrence of pelvic pain [12 months]

Secondary Outcome Measures

Metabolic effects [12 months]
Ovarian effects [12 months]
Endometrial effects [12 months]
Bleedings characteristics [12 months]
Protocol adherence [12 months]
Satisfaction rate [12 months]
Adverse events [12 months]
Effects on cognitive function and mood [12 months]
Quality of life [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Premenopausal state
Endometriosis-related chronic pelvic pain
Hystologically confirmed endometriosis at laparoscopy
Subjective severity of pelvic pain by using a visual analogue scale of at least 70
No immediate desire of pregnancy

Exclusion Criteria:

Age ≤18 or ≥ 40
Previous use of drugs for treating CPP (wash-out period of 3 months), with exclusion of non-steroidal anti-inflammatory drugs
Contraindication to estro-progestin compounds
Major medical diseases
Psychiatric disorders
Pelvic inflammatory disease
Adnexal patologies
Unability to complete the daily diary
History of alcohol or other drugs abuse