Comparing Two Medical Treatments for Early Pregnancy Failure.

Conditions

Early Pregnancy Failure

Keywords

miscarriage, mifepristone, misoprostol, medical treatment, patient satisfaction, abortifacient agents

Brief summary

This study aims to compare whether a combination of two drugs (Mifepristone and misoprostol) are superior compared to using only one of these drugs (Misoprostol) as medical treatment for a miscarriage. Women in whom early pregnancy failure, 6-14 weeks postmenstrual, is ultrasonographically confirmed qualify for this study. It is expected that the combination of Mifepristone and Misoprostol is more effective in reaching complete evacuation, and therefore can prevent more invasive treatment such as curettage.

Detailed description

This study will test the hypothesis that, in early pregnancy failure, the sequential combination of mifepristone with misoprostol is superior to the use of misoprostol alone in terms of complete evacuation of products of conception (primary outcome), patient satisfaction, complications, side effects and costs (secondary outcomes). The trial will be performed multi-centred (hospitals), prospectively, two-armed, randomized, double-blinded and placebo-controlled. Women with ultrasonographically confirmed early pregnancy failure (6-14 weeks postmenstrual), managed expectantly for at least one week, can be included. Before medical treatment with misoprostol (two doses 400mcg (four hours apart), repeated after 24 hours if no tissue is lost), patients will be randomized to oral mifepristone (600mg) or oral placebo (identical in appearance). The investigators aim to randomize 460 women in a 1:1 ratio, stratified by centre. After six weeks, the primary endpoint, complete or incomplete evacuation, will be determined

Charlotte C. Hamel, S.F.P.J. Coppus, Joyce van den Berg, Esther Hink, Jacoba van Seeters et al. (16 authors)

Fertility & Reproduction2022-09-011 citations

10.1142/s2661318222740115

Predicting the likelihood of successful medical treatment of early pregnancy loss: development and internal validation of a clinical prediction model

Charlotte C. Hamel, Priya Vart, Frank P.H.A. Vandenbussche, D.D.M. Braat, Marcus P. Snijders et al. (6 authors)

Human Reproduction2022-03-089 citations

10.1093/humrep/deac048

Mifepristone followed by misoprostol compared with placebo followed by misoprostol as medical treatment for early pregnancy loss (the Triple M trial): A double-blind placebo-controlled randomised trial.

Hamel C, Coppus S, van den Berg J, Hink E, van Seeters J, van Kesteren P, Merién A, Torrenga B, van de Laar R, Terwisscha van Scheltinga J, Gaugler-Senden I, Graziosi P, van Rumste M, Nelissen E, Vandenbussche F, Snijders M.

2021-01-0618 citations

10.1016/j.eclinm.2020.100716

Mifepristone and misoprostol versus misoprostol alone for uterine evacuation after early pregnancy failure: study protocol for a randomized double blinded placebo-controlled comparison (Triple M Trial)

Joyce van den Berg, Charlotte C. Hamel, Marcus P. Snijders, S.F.P.J. Coppus, Frank P.H.A. Vandenbussche

BMC Pregnancy and Childbirth2019-11-2714 citations

10.1186/s12884-019-2497-y

Interventions

DRUGMifepristone

Adding 600 mg of Mifepristone to the regular treatment with Misoprostol 800 mcg.

DRUGMisoprostol

Regular treatment with Misoprostol 800 mcg.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Caregiver)

Intervention model description

Before medical treatment with misoprostol (two doses 400mcg (four hours apart), repeated after 24 hours if no tissue is lost), patients will be randomized to oral mifepristone (600mg) or oral placebo (identical in appearance).

Eligibility

Sex/Gender

FEMALE

Age

16 Years to No maximum

Healthy volunteers

No

Inclusion criteria

Early pregnancy failure, 6-14 weeks postmenstrual with * a crown-rump length ≥ 6mm and no cardiac activity OR * a crown-rump length \<6mm and no fetal growth at least one week later OR * a gestational sac with absent embryonic pole for at least one week. * At least one week after diagnosis OR a discrepancy of at least one week between crown-rump length and calendar gestational age * Intra-uterine pregnancy * Women aged above 16 years * Hemodynamic stable patient * No signs of infection * No signs of incomplete abortion * No contraindications for mifepristone or misoprostol

Exclusion criteria

* Patient does not meet inclusion criteria, discovered after randomization * Inability to give informed consent * Known clotting disorder or use of anticoagulants * Known risk factors for, or presence of, a cardiovascular disease * Language barrier

Design outcomes

Primary

Measure	Time frame	Description
Complete evacuation	six weeks after initial treatment	Whether or not complete evacuation (total endometrial thickness \<15 mm) has been acquired will be assessed through ultrasonography.

Secondary

Measure	Time frame	Description
patient satisfaction	At baseline, day four, two and six weeks after treatment	To assess how satisfied patient are with the treatment they underwent. Patient satisfaction with treatment will be measured using The Client Satisfaction Questionnaire (CSQ-8, digital)
complications	six weeks after treatment	How many and which complications have occured?
side effects	six weeks after treatment	Which side effects have patients experienced and to what degree?
costs	up to six weeks after treatment	To evaluate which medical treatment strategy is cost-effective, volumes of health care consumed will additionally be measured prospectively alongside the clinical trial together with cost associated with productivity losses. Costs of medical interventions (direct costs) and costs resulting from productivity loss (indirect costs) will be taken into account. Resource uses will be recorded in the case report forms. Standardized unit costs will be calculated using the Dutch manual for costing in economic evaluations and standardised costs.
Overall quality of health, as experienced by the patient.	At baseline, day four, and two and six weeks after initial treatment.	To measure the quality of the health status of the patients, a validated so-called health-related quality of life (HRQoL) instrument will be used: the Short Form 36 health survey

Countries

Netherlands

Outcome results

None listed