NATIONAL CLINICAL TRIAL BASE OF CHINESE MEDICINE 《国家中医临床研究基地》妇科慢病项目 Protocol Final Version Effect of Acupuncture and Clomiphene Citrate on Live Birth in Anovulatory Women with Polycystic Ovary Syndrome: a Randomized Controlled Trial （NCT01573858，ChiCTR-TRC-12002081） Funded by State Administration of Traditional Chinese Medicine January 15, 2013 Downloaded From: https://jamanetwork.com/ on 09/30/2021 PCOSAct Protocol 8.1 CONTENTS 1. Committee composition ...................................................................................................... 4 1.1 Protocol committee .................................................................................................... 4 1.2 Steering Committee ................................................................................................... 4 1.3 Data Coordination Committee .................................................................................. 7 1.4 Publication Committee .............................................................................................. 7 2. Background .......................................................................................................................... 8 3. Objectives ............................................................................................................................ 11 4. Study procedures ............................................................................................................... 12 4.1 Pre-screening ............................................................................................................. 12 4.2 Screening Visit (Visit 1: physician) ............................................................................ 12 4.3 Baseline Visit ............................................................................................................. 12 4.4 Weekly acupuncture Visit: ....................................................................................... 13 4.5 Weekly Serum Progesterone Level and Pregnancy Test ........................................ 13 4.6 Pregnancy Visits (only with conception) ................................................................. 13 4.7 End of Treatment Visit .............................................................................................. 13 5. Study design ....................................................................................................................... 14 6. Subject selection and exclusion ........................................................................................ 14 7. Inclusion criteria ................................................................................................................. 14 8. Exclusion criteria ................................................................................................................ 14 9. Recruitment and Strategy ................................................................................................. 16 9.1 Hospital/Local Health Care Referrals ....................................................................... 16 9.2 Local Publicity Office ................................................................................................ 16 9.3 Local Advertisements ............................................................................................... 16 10. Prescreening ..................................................................................................................... 17 11. Screening Visit .................................................................................................................... 17 12. Physical Examination ......................................................................................................... 17 13. Transvaginal Ultrasound Examination and menstrual cyclicity ...................................... 18 14. Laboratory Examination ................................................................................................... 19 The Central Laboratory: Heilongjiang University of Chinese Medicine Laboratory .... 19 15. Quality of Life Measures (QOL) ....................................................................................... 20 16. Exclusion of Other Infertility Factors .............................................................................. 20 17. Preconception Counseling ................................................................................................ 21 18. Screen Failures .................................................................................................................. 22 19. Counseling about Menstrual and Intercourse Diaries ..................................................... 22 20. Adjuvant Therapy ............................................................................................................. 22 21. Progestin Withdrawal ....................................................................................................... 22 22. Study Specific Procedures/Visits ...................................................................................... 23 22.1 Screening Visit: ........................................................................................................ 23 22.2 Baseline Visit: ......................................................................................................... 24 22.3 Weekly acupuncture Visit ...................................................................................... 24 23. Cycle treatment program ................................................................................................ 25 23.1 Non-Responders ...................................................................................................... 25 23.2 Responders ............................................................................................................ 26 23.3 Pregnancy ............................................................................................................... 27 23.4 Dispensing of Study Drug before Every Cycle ....................................................... 27 23.5 Breaks in Study Protocol ........................................................................................ 27 1 Downloaded From: https://jamanetwork.com/ on 09/30/2021 PCOSAct Protocol 8.1 23.6 Pregnancy Visits ..................................................................................................... 28 23.7 End of Treatment Visit ........................................................................................... 28 23.8 Final Pregnancy Outcome data ............................................................................. 28 24. Randomization ................................................................................................................ 29 25. Treatment Arms ............................................................................................................... 29 25.1 Acupuncture protocols 1 and 2 .............................................................................. 29 25.2 Clomiphene citrate (CC) and Placebo CC ............................................................... 31 25.3 Study Drugs packaged and dispensed ................................................................... 31 26. Monitoring ........................................................................................................................ 32 27. Outcome measures ........................................................................................................... 32 27.1 Primary outcomes: Live birth rate ......................................................................... 32 27.2 Secondary outcomes: ............................................................................................. 32 28. Timeline and Recruitment Plan ........................................................................................ 32 29. Statistics ........................................................................................................................... 33 29.1 Statistical tests ....................................................................................................... 33 29.2 Sample size estimation .......................................................................................... 33 30. References ....................................................................................................................... 34 31. Assessment of safety, quality control and quality assurance ........................................ 37 31.1 Safety analysis ......................................................................................................... 37 31.2 Interim Analysis ...................................................................................................... 37 32. Data and Safety Monitoring Board (DSMB) and Ethics ................................................. 37 32.1 DSMB ...................................................................................................................... 37 32.2 DSMB Members ..................................................................................................... 38 32.3 Ethics ...................................................................................................................... 38 33. Data Handling and record keeping ................................................................................. 38 33.1 Data Entry and Forms ............................................................................................. 39 33.2 Data Security .........................................................................................................