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Trial record 27 of 68 for:    Amenorrhea: Clinical Trials

"Stair Step Study"

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ClinicalTrials.gov Identifier: NCT03309176
Recruitment Status : Completed
First Posted : October 13, 2017
Last Update Posted : June 5, 2018
Sponsor:
Information provided by (Responsible Party):
Radboud University

Brief Summary:

Rationale:

There is some information suggesting that a progesterone-induced withdrawal bleeding before the start of ovulation induction in women suffering from oligo- or amenorrhea reduces pregnancy and live birth rate.

Objective:

To evaluate the effects of withholding progesterone-induced endometrial withdrawal bleeding before ovulation induction on the time to pregnancy and the ongoing pregnancy rate.

Study design:

Prospective multicenter randomized controlled feasibility study

Study population:

Women with oligomenorrhea or amenorrhea according to WHO classification category 2

Intervention:

Patients will be randomized to receive one of the following two treatments:

Stair step group: blind start ovulation induction (no progesterone induced withdrawal bleeding and stair step protocol in case of treatment failure.

Control: standard care; a progesterone induced withdrawal bleeding in case of no spontaneous menses before starting an ovulation induction cycle and in between anovulatory cycles.

Main study parameters/endpoints:

The primary endpoints are the time to pregnancy and ongoing pregnancy rate within a treatment horizon of 3 cycles. Secondary endpoints include time to ovulation, endometrial thickness, multiple pregnancy and the incidence of treatment failure.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The number of site visits or physical examinations will not differ from accepted clinical practice.


Condition or disease Intervention/treatment Phase
Ovulation Disorder Drug: Medroxyprogesterone Acetate 10 MG Other: Stair step protocol without Medroxyprogesterone Acetate Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Stair step group: blind start ovulation induction (no progesterone induced withdrawal bleeding and stair step protocol in case of treatment failure.

Control: standard care; a progesterone induced withdrawal bleeding in case of no spontaneous menses before starting an ovulation induction cycle and in between anovulatory cycles.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Is Endometrial Withdrawal Bleeding Necessary Prior to Ovulation Induction With Clomiphene Citrate? A Randomized Controlled Trial and Feasibility Study
Actual Study Start Date : June 21, 2016
Actual Primary Completion Date : November 30, 2017
Actual Study Completion Date : May 31, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Standard group
Intervention:Medroxyprogesterone acetate (Provera) 10 mg daily for 10 days will be used prior to starting ovulation induction with clomiphene citrate (CC) and between anovulatory cycles. On cycle day (CD) 3 CC 50 mg is administered daily for 5 days. Follicle growth will be monitored by ultrasound, starting from CD11. Anovulatory patients (defined as no follicle ≥ 14 mm) on CD20, will receive Provera 10mg daily for 10 days. The CC dosage will be increased in the next cycle. On CD3 patients will receive CC 100 mg daily for 5 days with ultrasounds performed from CD11 onwards. Anovulatory patients will receive Provera 10mg daily for 10 days. In the next cycle the CC dose will be increased to 150 mg, starting from CD3, daily for 5 days with ultrasounds starting from CD11-20.
Drug: Medroxyprogesterone Acetate 10 MG
Patients in the standard arm will receive Medroxyprogesterone Acetate 10mg daily for 10 days prior to the first ovulation induction cycle and in between anovulatory cycles.
Other Name: Provera

Experimental: Stair Step group
Intervention: Stair step protocol without medroxyprogesterone acetate 10 mg prior to ovulation induction with clomiphene citrate (CC), nor in between anovulatory cycles. After performing an ultrasound to check for the presence of cysts or any other abnormalities and a negative pregnancy test, patients will receive CC 50 mg daily for 5 days. Ultrasounds will be performed on CD11-14. If there is no response on CD14 (no follicle ≥ 14 mm), the dose of CC is immediately increased to 100 mg CC daily for 5 days and an ultrasound is performed 1 week following the last ultrasound. If there is no response, 150 mg CC daily is initiated immediately for 5 days and the ultrasound is repeated 1 week after the previous ultrasound.
Other: Stair step protocol without Medroxyprogesterone Acetate
No administration of Medroxyprogesterone Acetate prior to each cycle. Stair step method: rapidly increasing the dose of clomiphene citrate in case of no follicular response
Other Name: Stair step




Primary Outcome Measures :
  1. Ongoing pregnancy rate per cycle [ Time Frame: in case of pregnancy: 8 weeks after the start of each cycle, (maximum of 3 cycles, duration of 1 cycle: 28-35 days) ]
    Ongoing pregnancy is defined as the presence of at least one intra uterine fetus with heartbeat at 8 weeks of gestation

  2. Time to pregnancy [ Time Frame: duration of 1 cycle: 28-35 days, a maximum of 3 cycles will be performed (pregnancy test will be performed at the end of the cycle if there is no menstruation) ]
    the time between obtaining informed consent and the presence of a positive pregnancy test after treatment


Secondary Outcome Measures :
  1. Time to ovulation [ Time Frame: 3 cycles of 28-35 days, calculated as 14 days before the start of menstruation or 14 days before a positive pregnancy test ]
    calculated as 14 days prior to the first day of menstruation or positive pregnancy test

  2. Endometrial thickness on the last day of ultrasonography [ Time Frame: maximum of 3 cycles (each 28-35 days) ]
    measurement of the endometrial thickness on the last day of ultrasound monitoring. This day can differ among cycles, depending on the speed of follicle growth, hence it cannot be further specified.

  3. The incidence of multiple follicle growth on the last day of ultrasonography [ Time Frame: maximum of 3 cycles (each 28-35 days) ]
    This day can differ among cycles, depending on the speed of follicle growth, hence it cannot be further specified.

  4. The incidence of multiple pregnancy [ Time Frame: in case of pregnancy: 8 weeks after the start of a treatment cycle (maximum of 3 cycles; each 28-35 days) ]
    ultrasound performed at 8 weeks of gestation, which is 8 weeks after the start of a treatment cycle

  5. The incidence of treatment failure [ Time Frame: maximum of 3 cycles (each 28-35 days) ]
    treatment failure is defined as no follicle ≥ 14 mm on CD 20 despite using a maximum clomiphene citrate dose of 150 mg in the standard arm. Or no follicle ≥ 14 mm after increasing the clomiphene citrate dose up to 150 mg.

  6. The number of eligible patients [ Time Frame: Inclusion 16 months, follow-up 3 months. ]
    The total number of patients that fits the inclusion criteria.

  7. The number of protocol violations [ Time Frame: duration: maximum of 3 cycles (each 28-35 days) ]
    The total number of protocol violations.



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Ages Eligible for Study:   18 Years to 41 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • WHO classification category 2 PCOS or non-PCOS
  • Age between 18 - 41 years
  • Patent Fallopian tubes, proven by hysterosalpingography (HSG), a negative Chlamydia antibody titre (CAT) or diagnostic laparoscopy combined with tubal testing (DLS and TT), depending on the local protocol.
  • BMI < 40 kg/m2

Exclusion Criteria:

  • BMI > 40 kg/m2
  • Previous unsuccessful ovulation induction cycles with CC
  • Double-sided tubal pathology
  • Presence of ovarian cysts on ultrasound
  • Moderate - severe male infertility (TMSC < 3 million)
  • Grade III/IV endometriosis
  • Thrombosis
  • Severe liver disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03309176


Locations
Netherlands
Gelderse Vallei Hospital
Ede, Gelderland, Netherlands
Canisius-Wilhelmina Hospital
Nijmegen, Gelderland, Netherlands
Radboud University Medical Center
Nijmegen, Gelderland, Netherlands
Sponsors and Collaborators
Radboud University

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03309176     History of Changes
Other Study ID Numbers: NL56254.091.15
First Posted: October 13, 2017    Key Record Dates
Last Update Posted: June 5, 2018
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Citric Acid
Clomiphene
Enclomiphene
Zuclomiphene
Medroxyprogesterone
Medroxyprogesterone Acetate
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Contraceptive Agents, Male
Antineoplastic Agents, Hormonal
Antineoplastic Agents