Chia-Shi Wang1, Curtis Travers2, Courtney McCracken2, Traci Leong3, Rasheed Gbadegesin4, Alejandro Quiroga5, Mark R Benfield6, Guillermo Hidalgo7, Tarak Srivastava8, Megan Lo9, Ora Yadin10, Robert Mathias11, Carlos E Araya11, Myda Khalid12, Alvaro Orjuela13, Joshua Zaritsky14, Samhar Al-Akash15, Margret Kamel2, Larry A Greenbaum16. 1. Department of Pediatrics, Emory and Children's Pediatric Institute, Atlanta, Georgia; chia-shi.wang@emory.edu wang.couk@gmail.com. 2. Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia. 3. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia. 4. Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina. 5. Department of Pediatrics and Human Development, Helen DeVos Children's Hospital, Grand Rapids, Michigan. 6. Pediatric Nephrology of Alabama, PC, Birmingham, Alabama. 7. Department of Pediatrics, East Carolina University, Greenville, North Carolina. 8. Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri. 9. Department of Pediatrics, Medical College of Virginia School of Medicine, Virginia Commonwealth University, Richmond, Virginia. 10. Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles Mattel Children's Hospital, Los Angeles, California. 11. Department of Pediatrics, Nemours Children's Hospital, Orlando, Florida. 12. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana. 13. Department of Pediatrics, Baylor College of Medicine, Houston, Texas. 14. Department of Pediatrics, A.I. DuPont Hospital for Children/ Nemours, Wilmington, Delaware; and. 15. Driscoll Children's Hospital, Corpus Christi, Texas. 16. Department of Pediatrics, Emory and Children's Pediatric Institute, Atlanta, Georgia.
Abstract
BACKGROUND AND OBJECTIVES: There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 toACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. RESULTS: The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. CONCLUSIONS:ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.
RCT Entities:
BACKGROUND AND OBJECTIVES: There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. RESULTS: The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. CONCLUSIONS:ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.
Authors: Jonathan Hogan; Andrew S Bomback; Kshama Mehta; Pietro A Canetta; Maya K Rao; Gerald B Appel; Jai Radhakrishnan; Richard A Lafayette Journal: Clin J Am Soc Nephrol Date: 2013-09-05 Impact factor: 8.237
Authors: Andrew S Bomback; James A Tumlin; Joel Baranski; James E Bourdeau; Anatole Besarab; Alice S Appel; Jai Radhakrishnan; Gerald B Appel Journal: Drug Des Devel Ther Date: 2011-03-14 Impact factor: 4.162