Clinical Trial Results:
Efficacy of Very Early Medical Abortion – a randomized controlled non-inferiority trial
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Summary
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EudraCT number |
2018-003675-35 |
Trial protocol |
SE FI AT DK |
Global end of trial date |
06 Jun 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Feb 2025
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First version publication date |
27 Feb 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
WV2018
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Karolinska Institutet
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Sponsor organisation address |
Nobels väg 6, Solna, Sweden, 17177
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Public contact |
Kristina Gemzell Danielsson, Karolinska Instituet, 46 08517700002128, kristina.gemzell@ki.se
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Scientific contact |
Kristina Gemzell Danielsson, Karolinska Instituet, 46 08517700002128, kristina.gemzell@ki.se
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 May 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Jun 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Jun 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To investigate is if the efficacy of VEMA is non-inferior within a non-inferiority margin of 3 percent to delayed abortion treatment initiated when an intrauterine pregnancy (IUP) can be confirmed on ultrasound?
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Protection of trial subjects |
The trial protocol was approved by the Swedish Ethical Review Authority and local ethics committee at each trial site or in each country. Participants were included after providing written informed consent. An external monitor and data and safety monitoring board were appointed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Mar 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Sweden: 668
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Country: Number of subjects enrolled |
Austria: 2
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Country: Number of subjects enrolled |
Denmark: 57
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Country: Number of subjects enrolled |
Finland: 92
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Country: Number of subjects enrolled |
Australia: 23
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Country: Number of subjects enrolled |
Norway: 24
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Country: Number of subjects enrolled |
New Zealand: 199
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Country: Number of subjects enrolled |
Nepal: 400
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Country: Number of subjects enrolled |
United Kingdom: 39
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Worldwide total number of subjects |
1504
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EEA total number of subjects |
843
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1504
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial took place at 26 sites in nine countries from March 2019 through April 2023. Women seeking medication abortion with a maximum estimated gestational length of 42 days and an unconfirmed intrauterine pregnancy on vaginal ultrasound examination were screened for inclusion. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Women were eligible if they were 18 years of age or older, spoke English or a local language, and provided informed consent. Exclusion criteria were symptoms or signs of pathologic pregnancy, risk factors for ectopic pregnancy or any contraindications to medication abortion. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Very Early Medical Abortion (VEMA) | |||||||||||||||||||||
Arm description |
Participants in the early-start group initiated medication abortion on the day of or the day after trial inclusion. | |||||||||||||||||||||
Arm type |
Intervention, early treatment (VEMA) | |||||||||||||||||||||
Investigational medicinal product name |
mifepristone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All the participants received the World Health Organization–recommended protocol for medication abortion: mifepristone at a dose of 200 mg orally, followed 24 to 48 hours later by misoprostol at a dose of 800 μg administered vaginally, sublingually, or buccally according to local standard practice. An additional dose of misoprostol (400 μg) was administered if bleeding
had not started within 3 hours (except in Australia). Oral analgesia was offered according to local clinical routine with a combination of nonsteroidal antiinflammatory drugs and paracetamol with repeat doses or oral opioids (or both) if needed.
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Arm title
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Standard | |||||||||||||||||||||
Arm description |
Treatment for participants in the standard group was delayed until a repeat ultrasound examination on trial day 7 (with a window of ±2 days) visualized an intrauterine pregnancy. | |||||||||||||||||||||
Arm type |
Standard intervention | |||||||||||||||||||||
Investigational medicinal product name |
mifepristone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All the participants received the World Health Organization–recommended protocol for medication abortion: mifepristone at a dose of 200 mg orally, followed 24 to 48 hours later by misoprostol at a dose of 800 μg administered vaginally, sublingually, or buccally according to local standard practice. An additional dose of misoprostol (400 μg) was administered if bleeding
had not started within 3 hours (except in Australia). Oral analgesia was offered according to local clinical routine with a combination of nonsteroidal antiinflammatory drugs and paracetamol with repeat doses or oral opioids (or both) if needed.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 1504 participants were initially enrolled - 754 assigned to Very early medication abortion (VEMA), however 13 were excluded prior to treatment - 750 were assigned to Standard medication abortion but 26 were excluded prior to treatment. |
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Baseline characteristics reporting groups
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Reporting group title |
Very Early Medical Abortion (VEMA)
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Reporting group description |
Participants in the early-start group initiated medication abortion on the day of or the day after trial inclusion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard
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Reporting group description |
Treatment for participants in the standard group was delayed until a repeat ultrasound examination on trial day 7 (with a window of ±2 days) visualized an intrauterine pregnancy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Very Early Medical Abortion (VEMA)
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Reporting group description |
Participants in the early-start group initiated medication abortion on the day of or the day after trial inclusion. | ||
Reporting group title |
Standard
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Reporting group description |
Treatment for participants in the standard group was delayed until a repeat ultrasound examination on trial day 7 (with a window of ±2 days) visualized an intrauterine pregnancy. | ||
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End point title |
Complete abortion without ongoing pregnancy or surgical intervention | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Per protocol
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Statistical analysis title |
Risk difference STANDARD-VEMA | |||||||||
Comparison groups |
Very Early Medical Abortion (VEMA) v Standard
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Number of subjects included in analysis |
1398
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||
P-value |
= 0.9 | |||||||||
Method |
Proportion test | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
-0.1
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-2.4 | |||||||||
upper limit |
2.1 | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Per protocol
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
NA
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Reporting groups
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Reporting group title |
Overall study
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/39504520 |
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