Ulipristal acetate versus placebo for fibroid treatment before surgery
Jacques Donnez, Tetyana F Tatarchuk, Philippe Bouchard, Lucian Puscasiu, Nataliya F Zakharenko, Tatiana Ivanova, Gyula Ugocsai, Michal Mara, Manju P Jilla, Elke Bestel, Paul Terrill, Ian Osterloh, Ernest Loumaye, PEARL I Study Group, David H Barlow, Christine Bergeron, Elke Bestel, Vitaly Bezhenar, Philippe Bouchard, Doru-Ioan Craiut, Roman Chmel, Valeriu Cornea, Jacques Donnez, Hema Divakar, Mihai Cristian Dumitrascu, Bart C J M Fauser, Alex Ferenczy, Irina Y Ganzhiy, Laszlo Hagymasy, Robert Hudecek, Decebal Hudita, Alexey Ilin, Tatiana Ivanova, Vijayaraghavan Jaya, Manju P Jilla, Richard Kay, Eduard Komlichenko, Alla G Kornatska, Mikhail Korshunov, Victor Kostenko, Valentina P Kvashenko, Ádám László, Veronique Lecomte, Ernest Loumaye, Marketa Mannering, Michal Mara, Jo Marshall, Klim McPherson, Mihaly Molnar, Edward Morris, Ian Osterloh, Sadhana Patwardhan, Norbert W Paul, Tatyana V Pekhno, Valentin O Potapov, Lucian Puscasiu, Vira I Pyrogova, Ivan Reich, Chaitanya Shembekar, Pal Siklos, Zsolt Szeberenyi, Virginia Tarlea, Tetyana F Tatarchuk, Paul Terrill, Marat Tugushev, Rajani Uday, Gyula Ugocsai, Alistair R W Williams, Nataliya F Zakharenko, Dominique de Ziegler, Tatiana Zykova, Jacques Donnez, Tetyana F Tatarchuk, Philippe Bouchard, Lucian Puscasiu, Nataliya F Zakharenko, Tatiana Ivanova, Gyula Ugocsai, Michal Mara, Manju P Jilla, Elke Bestel, Paul Terrill, Ian Osterloh, Ernest Loumaye, PEARL I Study Group, David H Barlow, Christine Bergeron, Elke Bestel, Vitaly Bezhenar, Philippe Bouchard, Doru-Ioan Craiut, Roman Chmel, Valeriu Cornea, Jacques Donnez, Hema Divakar, Mihai Cristian Dumitrascu, Bart C J M Fauser, Alex Ferenczy, Irina Y Ganzhiy, Laszlo Hagymasy, Robert Hudecek, Decebal Hudita, Alexey Ilin, Tatiana Ivanova, Vijayaraghavan Jaya, Manju P Jilla, Richard Kay, Eduard Komlichenko, Alla G Kornatska, Mikhail Korshunov, Victor Kostenko, Valentina P Kvashenko, Ádám László, Veronique Lecomte, Ernest Loumaye, Marketa Mannering, Michal Mara, Jo Marshall, Klim McPherson, Mihaly Molnar, Edward Morris, Ian Osterloh, Sadhana Patwardhan, Norbert W Paul, Tatyana V Pekhno, Valentin O Potapov, Lucian Puscasiu, Vira I Pyrogova, Ivan Reich, Chaitanya Shembekar, Pal Siklos, Zsolt Szeberenyi, Virginia Tarlea, Tetyana F Tatarchuk, Paul Terrill, Marat Tugushev, Rajani Uday, Gyula Ugocsai, Alistair R W Williams, Nataliya F Zakharenko, Dominique de Ziegler, Tatiana Zykova
Abstract
Background: The efficacy and safety of oral ulipristal acetate for the treatment of symptomatic uterine fibroids before surgery are uncertain.
Methods: We randomly assigned women with symptomatic fibroids, excessive uterine bleeding (a score of >100 on the pictorial blood-loss assessment chart [PBAC, an objective assessment of blood loss, in which monthly scores range from 0 to >500, with higher numbers indicating more bleeding]) and anemia (hemoglobin level of ≤10.2 g per deciliter) to receive treatment for up to 13 weeks with oral ulipristal acetate at a dose of 5 mg per day (96 women) or 10 mg per day (98 women) or to receive placebo (48 women). All patients received iron supplementation. The coprimary efficacy end points were control of uterine bleeding (PBAC score of <75) and reduction of fibroid volume at week 13, after which patients could undergo surgery.
Results: At 13 weeks, uterine bleeding was controlled in 91% of the women receiving 5 mg of ulipristal acetate, 92% of those receiving 10 mg of ulipristal acetate, and 19% of those receiving placebo (P<0.001 for the comparison of each dose of ulipristal acetate with placebo). The rates of amenorrhea were 73%, 82%, and 6%, respectively, with amenorrhea occurring within 10 days in the majority of patients receiving ulipristal acetate. The median changes in total fibroid volume were -21%, -12%, and +3% (P=0.002 for the comparison of 5 mg of ulipristal acetate with placebo, and P=0.006 for the comparison of 10 mg of ulipristal acetate with placebo). Ulipristal acetate induced benign histologic endometrial changes that had resolved by 6 months after the end of therapy. Serious adverse events occurred in one patient during treatment with 10 mg of ulipristal acetate (uterine hemorrhage) and in one patient during receipt of placebo (fibroid protruding through the cervix). Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently than with placebo.
Conclusions: Treatment with ulipristal acetate for 13 weeks effectively controlled excessive bleeding due to uterine fibroids and reduced the size of the fibroids. (Funded by PregLem; ClinicalTrials.gov number, NCT00755755.).
Source: PubMed