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Clinical Trial
. 2018 Dec 7;13(12):1859-1865.
doi: 10.2215/CJN.06890618. Epub 2018 Nov 15.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial

Chia-Shi Wang  1 , Curtis Travers  2 , Courtney McCracken  2 , Traci Leong  3 , Rasheed Gbadegesin  4 , Alejandro Quiroga  5 , Mark R Benfield  6 , Guillermo Hidalgo  7 , Tarak Srivastava  8 , Megan Lo  9 , Ora Yadin  10 , Robert Mathias  11 , Carlos E Araya  11 , Myda Khalid  12 , Alvaro Orjuela  13 , Joshua Zaritsky  14 , Samhar Al-Akash  15 , Margret Kamel  2 , Larry A Greenbaum  1
Affiliations
Clinical Trial

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial

Chia-Shi Wang et al. Clin J Am Soc Nephrol. .

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 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.

Keywords: Adrenocorticotropic Hormone; Childhood Nephrotic Syndrome; children; clinical trial; nephrotic syndrome.

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Figures

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Graphical abstract
Figure 1.
Figure 1.
Participant flow through the ATLANTIS trial comparing ACTH with no relapse-preventing treatment with the option of crossover.
See this image and copyright information in PMC

Comment in

  • Does What Goes Around Always Come Around?
    Trachtman H. Trachtman H. Clin J Am Soc Nephrol. 2018 Dec 7;13(12):1788-1790. doi: 10.2215/CJN.12291018. Epub 2018 Nov 15. Clin J Am Soc Nephrol. 2018. PMID: 30442862 Free PMC article. No abstract available.

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