Nieman 2011.
| Methods | Single‐centre blinded placebo RCT | |
| Participants | Participants randomised to 1 of 3 groups in a 1:1:1 ratio (n = 42) ‐ 14 ulipristal acetate 10 mg, 1 withdrawn, 13 analysed ‐ 14 ulipristal acetate 20 mg, 1 withdrawn, 13 analysed ‐ 14 placebo, 2 withdrawn, 12 analysed Baseline demographics similar in each group Inclusion criteria ‐ Symptomatic fibroids > 2 cm in diameter (MRI) ‐ Age 25 to 50 years ‐ Ovulatory menstrual cycles of 24 to 35 days ‐ Haemoglobin > 10 g/dL ‐ Creatinine < 1.3 mg/dL ‐ Liver function tests within 130% of upper normal range ‐ BMI < 35 kg/m2 Exclusion criteria ‐ Use of glucocorticoids or megestrol within 1 year ‐ Cervical dysplasia ‐ Adnexal mass ‐ Previous malignancy ‐ Inability to complete study requirements ‐ Serum FSH > 20 U/L ‐ Anovulation ‐ Rapidly growing fibroid ‐ Unexplained vaginal bleeding ‐ Pregnancy ‐ Lactation ‐ Use of hormonal compounds within 8 weeks of study start ‐ Therapy affecting ovarian or hepatic function Setting: USA |
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| Interventions | Ulipristal acetate 10 mg or 20 mg orally daily vs placebo Duration ‐ 3 menstrual cycles or 90 to 102 days if amenorrhoeic ‐ Initiated on cycle day 1 to 2 ‐ After initial treatment, women could elect hysterectomy, myomectomy or a second 3‐month treatment with ulipristal acetate 10 mg or 20 mg (part 2) ‐ Only part 1 of study included in this review |
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| Outcomes | Outcomes assessed at baseline and at end of treatment Primary outcome ‐ Fibroid MRI volume (formula for an ellipsoid) Secondary outcomes ‐ Bleeding (logs of daily vaginal bleeding) ‣ Amenorrhoea ‣ Change in Hgb and Hct ‐ Treatment‐dependent inhibition of ovulation ‐ QoL outcomes ‣ General QoL (SF‐36 version 2) ‣ Fibroid‐specific QoL (UFS‐QoL) ‐ Safety ‣ Adverse events ‣ Serum FSH, ACTH, cortisol, prolactin, LH, P4 and E2 (every 2 weeks) ‣ CBC, LFTs and acute care panel (every 4 weeks) ‣ Urine cortisol and creatinine excretion (days 20 to 30, 50 to 60 and 80 to 90) ‣ Endometrial hyperplasia (biopsy at treatment end). Used standard definition of PAEC provided by Mutter 2008 |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | “randomised participants to receive CDB‐2914 10 mg (CDB10) or 20 mg (CDB20), or a placebo (PLC), using computer‐generated blocks of six” |
| Allocation concealment (selection bias) | Low risk | Central randomisation and concealment but details unclear “The Pharmaceutical Development Service assured allocation concealment” However, this study used the same treatment design and allocation concealment service as the Levens study; details from the Levens study have been extrapolated here to grade this as low risk |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | “Laboratoire HRA‐Pharma provided 10‐mg CDB‐2914 tablets and a look alike inert placebo.Women received two bottles and were instructed to swallow one tablet from each bottle every morning before eating” |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Primary outcome was MRI measurements “PDS assured allocation concealment”, and this body seems to be at arms length from study “Women with paired MRI results were included in this ITT analysis even if they did not take all study medications” Participants were definitely blinded, so patient‐reported outcomes were blinded |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Missing outcome data balanced with plausible reasons. 1 drop‐out from each group after allocation “The baseline characteristics of these women were similar to study completers. Two women withdrew from treatment 2 because of inconvenience” Reasons for drop‐out were reported early in treatment (within 2 weeks of starting, 1 was on day 2) ‐ not lack of efficacy |
| Selective reporting (reporting bias) | Low risk | Study protocol available (NCT00290251) on clinical trials.gov; report includes all expected study outcomes |
| Other bias | Low risk | None identified |