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A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg.
Hum Reprod 2016; 31(3):530-40HR

Abstract

STUDY QUESTION

Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method?

SUMMARY ANSWER

Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population.

WHAT IS KNOWN ALREADY

LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception.

STUDY DESIGN, SIZE, DURATION

This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014.

PARTICIPANTS/MATERIALS, SETTING, METHODS

A total of 330 healthy fertile women aged 18-45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability questions were administered.

MAIN RESULTS AND THE ROLE OF CHANCE

There were 321 women included in the evaluable population (which includes all eligible women enrolled), with 141.9 woman-years (W-Y) of observation and with a rate (95% confidence interval [CI]) of 7.1 (3.8; 13.1) pregnancies per 100 W-Y of typical use (which reflects use of the study drug as main contraceptive method, but also includes possible use of other contraceptives from admission to end of study) and 7.5 (4.0; 13.9) pregnancies per 100 W-Y of sole use. In the primary evaluable population (which includes only eligible enrolled women <35 years old), the rate was 10.3 (5.4; 19.9) pregnancies per 100 W-Y of typical use, and 11.0 (5.7; 13.1) pregnancies per 100 W-Y of sole use. There were three reported severe adverse events and 102 other mild adverse events (most common were headache, nausea, abdominal and pelvic pain), with high recovery rate. The vaginal bleeding patterns showed a slight decrease in volume of bleeding and the number of bleeding-free days increased over time. There was only one case of severe anaemia, found at the final visit (0.4%). The method was considered acceptable, as over 90% of participants would choose to use it in the future or would recommend it to others.

LIMITATIONS, REASONS FOR CAUTION

This was a single-arm study with small sample size, without a control group, designed as a proof of concept study to explore the feasibility of this type of contraception.

WIDER IMPLICATIONS OF THE FINDINGS

A larger clinical study evaluating pericoital contraception with LNG is feasible and our data show that this method would be acceptable to many women.

STUDY FUNDING/COMPETING INTERESTS

This study received partial financial support from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR) and the World Health Organization. Gynuity and the Bill and Melinda Gates Foundation (BMGF) provided financial support for project monitoring. HRA Pharma donated the LNG product. N.K. was the initial project manager when she was with WHO/HRP and was employed by HRA Pharma, which distributes LNG for emergency contraception. The other authors declare no conflicts of interest.

TRIAL REGISTRATION NUMBER

This study was registered on ANZCTR, Trial ID ACTRN12611001037998.

TRIAL REGISTRATION DATE

4 October 2011.

DATE OF FIRST PATIENT'S ENROLMENT

10 January 2012.

Authors+Show Affiliations

Department of Reproductive Health and Research, World Health Organisation, Geneva, Switzerland festinma@who.int.Human Reproduction Unit, Department of Obstetrics and Gynaecology, University of Campinas, Campinas, Brazil.Department of Reproductive Health and Research, World Health Organisation, Geneva, Switzerland.Department of Reproductive Health and Research, World Health Organisation, Geneva, Switzerland.Department of Obstetrics and Gynaecology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.Department of Obstetrics and Gynaecology, National University Hospital, Singapore, Singapore.Department of Obstetrics and Gynaecology, National University Hospital, Singapore, Singapore.Department of Obstetrics and Gynaecology, Albert Szent-Gyorgyi Medical Centre, University of Szeged, Szeged, Hungary.Department of Obstetrics and Gynaecology, Albert Szent-Gyorgyi Medical Centre, University of Szeged, Szeged, Hungary.Human Reproduction Unit, Department of Obstetrics and Gynaecology, University of Campinas, Campinas, Brazil.Independent Consultant.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26830816

Citation

Festin, Mario P R., et al. "A Prospective, Open-label, Single Arm, Multicentre Study to Evaluate Efficacy, Safety and Acceptability of Pericoital Oral Contraception Using Levonorgestrel 1.5 Mg." Human Reproduction (Oxford, England), vol. 31, no. 3, 2016, pp. 530-40.
Festin MP, Bahamondes L, Nguyen TM, et al. A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg. Hum Reprod. 2016;31(3):530-40.
Festin, M. P., Bahamondes, L., Nguyen, T. M., Habib, N., Thamkhantho, M., Singh, K., ... Kapp, N. (2016). A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg. Human Reproduction (Oxford, England), 31(3), pp. 530-40. doi:10.1093/humrep/dev341.
Festin MP, et al. A Prospective, Open-label, Single Arm, Multicentre Study to Evaluate Efficacy, Safety and Acceptability of Pericoital Oral Contraception Using Levonorgestrel 1.5 Mg. Hum Reprod. 2016;31(3):530-40. PubMed PMID: 26830816.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg. AU - Festin,Mario P R, AU - Bahamondes,Luis, AU - Nguyen,Thi My Huong, AU - Habib,Ndema, AU - Thamkhantho,Manopchai, AU - Singh,Kuldip, AU - Gosavi,Arundhati, AU - Bartfai,Gyorgy, AU - Bito,Tamas, AU - Bahamondes,M Valeria, AU - Kapp,Nathalie, Y1 - 2016/01/31/ PY - 2015/05/12/received PY - 2015/12/07/accepted PY - 2016/2/3/entrez PY - 2016/2/3/pubmed PY - 2016/12/20/medline KW - anaemia KW - contraception KW - effectiveness KW - oral levonorgestrel KW - pericoital SP - 530 EP - 40 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 31 IS - 3 N2 - STUDY QUESTION: Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method? SUMMARY ANSWER: Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population. WHAT IS KNOWN ALREADY: LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception. STUDY DESIGN, SIZE, DURATION: This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 330 healthy fertile women aged 18-45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability questions were administered. MAIN RESULTS AND THE ROLE OF CHANCE: There were 321 women included in the evaluable population (which includes all eligible women enrolled), with 141.9 woman-years (W-Y) of observation and with a rate (95% confidence interval [CI]) of 7.1 (3.8; 13.1) pregnancies per 100 W-Y of typical use (which reflects use of the study drug as main contraceptive method, but also includes possible use of other contraceptives from admission to end of study) and 7.5 (4.0; 13.9) pregnancies per 100 W-Y of sole use. In the primary evaluable population (which includes only eligible enrolled women <35 years old), the rate was 10.3 (5.4; 19.9) pregnancies per 100 W-Y of typical use, and 11.0 (5.7; 13.1) pregnancies per 100 W-Y of sole use. There were three reported severe adverse events and 102 other mild adverse events (most common were headache, nausea, abdominal and pelvic pain), with high recovery rate. The vaginal bleeding patterns showed a slight decrease in volume of bleeding and the number of bleeding-free days increased over time. There was only one case of severe anaemia, found at the final visit (0.4%). The method was considered acceptable, as over 90% of participants would choose to use it in the future or would recommend it to others. LIMITATIONS, REASONS FOR CAUTION: This was a single-arm study with small sample size, without a control group, designed as a proof of concept study to explore the feasibility of this type of contraception. WIDER IMPLICATIONS OF THE FINDINGS: A larger clinical study evaluating pericoital contraception with LNG is feasible and our data show that this method would be acceptable to many women. STUDY FUNDING/COMPETING INTERESTS: This study received partial financial support from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR) and the World Health Organization. Gynuity and the Bill and Melinda Gates Foundation (BMGF) provided financial support for project monitoring. HRA Pharma donated the LNG product. N.K. was the initial project manager when she was with WHO/HRP and was employed by HRA Pharma, which distributes LNG for emergency contraception. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: This study was registered on ANZCTR, Trial ID ACTRN12611001037998. TRIAL REGISTRATION DATE: 4 October 2011. DATE OF FIRST PATIENT'S ENROLMENT: 10 January 2012. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/26830816/A_prospective_open_label_single_arm_multicentre_study_to_evaluate_efficacy_safety_and_acceptability_of_pericoital_oral_contraception_using_levonorgestrel_1_5_mg_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dev341 DB - PRIME DP - Unbound Medicine ER -