Emergency Contraception
Conditions
Keywords
Piroxicam, Levonorgestrel, Placebo, Randomised controlled control, Emergency contraception
Brief summary
This is a randomised controlled trial aimed at comparing the efficacy of levonorgestrel (LNG) co-administered with piroxicam or placebo for oral emergency contraception (EC). Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) commonly used as a pain-killer in inflammatory conditions. Efficacy will be measured as the percentage of pregnancies prevented.
Detailed description
Objective: To compare the percentage of pregnancies prevented by LNG co-administered with piroxicam or placebo for oral emergency contraception (EC) by a randomised controlled trial. Hypothesis to be tested: LNG plus piroxicam has higher percentage of pregnancies prevented compared with LNG plus placebo for oral emergency contraception. Design and subjects: This will be a prospective, randomised placebo-controlled clinical trial. Women attending the Family Planning Association of Hong Kong for oral EC within 72 hours of unprotected sexual intercourse will be recruited. Study instruments: Prospective follow-up of subjects in the clinic for the primary and secondary outcomes. Interventions: Eligible subjects will be randomised to receive one of the two treatment regimens, i.e. Group A: a single dose of LNG 1.5 mg and piroxicam 40 mg, or Group B: a single dose of LNG 1.5mg and placebo under direct supervision. Main outcome measures: Percentage of pregnancies prevented (PPP) is the primary outcome measure. Secondary outcome measures include failure rate, rate of occurrence of side effects and pattern of the menstruation following EC. Data analysis:The percentage of pregnancies prevented, failure rate and rate of occurrence of side effects will be compared between groups using Fisher-Exact test. Continuous variables regarding menstrual pattern between the two groups will be compared by Mann-Whitney U test. Expected results: LNG plus piroxicam has a higher PPP compared to LNG plus placebo.
Interventions
DRUGPiroxicam 40 mg
Additional co-treatment
Standard treatment
Sponsors
The Family Planning Association of Hong Kong
Dr. Hang Wun Raymond Li
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* healthy women aged 18 years or above; * requesting emergency contraception within 72 h of a single act of unprotected intercourse in the current menstrual cycle; * having menstrual cycles between 24 and 42 days * willing to abstain from further acts of unprotected intercourse and; * available for follow-up over the next 6 weeks.
Exclusion criteria
* post-abortion or postpartum and period have not yet returned, * being on prescription drugs currently * having unprotected intercourse in this cycle more than 72 hours or more than once before attending the clinic, * being found pregnant at the time of presentation, * breastfeeding, * having been sterilized (or partner having been sterilized) or having intrauterine contraceptive device in-situ, * uncertain about the date of the last menstrual period, * having used hormonal contraceptive (including EC pill) or NSAID in the current or past one cycle, * having history of asthma, urticarial or other allergic reactions to piroxicam, aspirin or other NSAIDs, * having history of ischaemic heart disease in the past one year * having history of pelvic ulcer disease and/or gastrointestinal bleeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Pregnancies Prevented | 1 month | (number of expected pregnancies - number of observed pregnancies) / number of expected pregnancies. The number of expected pregnancies is calculated based on the cycle day on which unprotected sexual intercourse occurred in each woman according to the model published by Trussel et al (Trussell J et al, Contraception 2003; 67:259-265). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pregnancy Rate | 1 month | number of participants who were pregnant / number of efficacy-evaluable participants |
Countries
Hong Kong
Participant flow
Recruitment details
A total of 860 women were recruited, all following the recruitment criteria, at the Family Planning Association of Hong Kong, between 20 August 2018 and 30 August 2022.
Pre-assignment details
No per-assignment drop-out.
Participants by arm
| Arm | Count |
|---|---|
| Piroxicam Piroxicam 40 mg (in 2 tablets) + levonorgestrel 1.5 mg single oral dose
430 women enrolled and received study drugs as per protocol. 12 lost to follow-up. 418 women who were efficacy-evaluable. | 430 |
| Placebo Placebo (2 tablets) + levonorgestrel 1.5 mg single oral dose
430 women enrolled and received study drugs as per protocol. 12 lost to follow-up. 418 women who were efficacy-evaluable. | 430 |
| Total | 860 |
Baseline characteristics
| Characteristic | Piroxicam | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 430 Participants | 430 Participants | 860 Participants |
| Age, Continuous | 32.6 years STANDARD_DEVIATION 5.9 | 31.9 years STANDARD_DEVIATION 5.8 | 32.2 years STANDARD_DEVIATION 5.9 |
| Body mass index | 21.7 kg/m^2 STANDARD_DEVIATION 3.3 | 21.9 kg/m^2 STANDARD_DEVIATION 3.4 | 21.8 kg/m^2 STANDARD_DEVIATION 3.3 |
| Coitus-treatment interval | 23.6 hours STANDARD_DEVIATION 15.2 | 24.4 hours STANDARD_DEVIATION 15.7 | 24.0 hours STANDARD_DEVIATION 15.5 |
| Race/Ethnicity, Customized African | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 8 Participants | 4 Participants | 12 Participants |
| Race/Ethnicity, Customized Chinese | 416 Participants | 417 Participants | 833 Participants |
| Race/Ethnicity, Customized Other Asians | 5 Participants | 8 Participants | 13 Participants |
| Region of Enrollment Hong Kong | 430 participants | 430 participants | 860 participants |
| Sex: Female, Male Female | 430 Participants | 430 Participants | 860 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 430 | 0 / 430 |
| other Total, other adverse events | 117 / 418 | 133 / 418 |
| serious Total, serious adverse events | 0 / 430 | 0 / 430 |
Outcome results
Primary
Percentage of Pregnancies Prevented
(number of expected pregnancies - number of observed pregnancies) / number of expected pregnancies. The number of expected pregnancies is calculated based on the cycle day on which unprotected sexual intercourse occurred in each woman according to the model published by Trussel et al (Trussell J et al, Contraception 2003; 67:259-265).
Time frame: 1 month
Population: efficacy-evaluable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Piroxicam | Percentage of Pregnancies Prevented | 94.7 percentage of pregnancies prevented |
| Placebo | Percentage of Pregnancies Prevented | 63.3 percentage of pregnancies prevented |
p-value: <0.000195% CI: [26.2, 36.4]Chi-squared
Secondary
Pregnancy Rate
number of participants who were pregnant / number of efficacy-evaluable participants
Time frame: 1 month
Population: Participants who completed follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Piroxicam | Pregnancy Rate | 1 Participants |
| Placebo | Pregnancy Rate | 7 Participants |
p-value: 0.03695% CI: [0.021, 0.906]Logistic regression, Firth's bias reduct