Design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease
Abstract Purpose Autosomal recessive polycystic kidney disease (ARPKD) is a hereditary condition characterized by massive kidney enlargement and developmental liver defects. Potential consequences during childhood include the need for kidney replacement therapy (KRT). We report the design of 2 ongoi...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12882-023-03072-x |
| _version_ | 1827984882853216256 |
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| author | Djalila Mekahli Max C. Liebau Melissa A. Cadnapaphornchai Stuart L. Goldstein Larry A. Greenbaum Mieczyslaw Litwin Tomas Seeman Franz Schaefer Lisa M. Guay-Woodford |
| author_facet | Djalila Mekahli Max C. Liebau Melissa A. Cadnapaphornchai Stuart L. Goldstein Larry A. Greenbaum Mieczyslaw Litwin Tomas Seeman Franz Schaefer Lisa M. Guay-Woodford |
| author_sort | Djalila Mekahli |
| collection | DOAJ |
| description | Abstract Purpose Autosomal recessive polycystic kidney disease (ARPKD) is a hereditary condition characterized by massive kidney enlargement and developmental liver defects. Potential consequences during childhood include the need for kidney replacement therapy (KRT). We report the design of 2 ongoing clinical trials (Study 204, Study 307) to evaluate safety, tolerability, and efficacy of tolvaptan in children with ARPKD. Methods Both trials are of multinational, multicenter, open-label design. Age range at enrollment is 28 days to < 12 weeks in Study 204 and 28 days to < 18 years in Study 307. Subjects in both studies must have a clinical diagnosis of ARPKD, and those in Study 204 must additionally have signs indicative of risk of rapid progression to KRT, namely, all of: nephromegaly, multiple kidney cysts or increased kidney echogenicity suggesting microcysts, and oligohydramnios or anhydramnios. Target enrollment is 20 subjects for Study 204 and ≥ 10 subjects for Study 307. Results Follow-up is 24 months in Study 204 (with optional additional treatment up to 36 months) and 18 months in Study 307. Outcomes include safety, tolerability, change in kidney function, and percentage of subjects requiring KRT relative to historical data. Regular safety assessments monitor for possible adverse effects of treatment on parameters such as liver function, kidney function, fluid balance, electrolyte levels, and growth trajectory, with increased frequency of monitoring following tolvaptan initiation or dose escalation. Conclusions These trials will provide data on tolvaptan safety and efficacy in a population without disease-specific treatment options. Trial registration Study 204: EudraCT 2020–005991-36; Study 307: EudraCT 2020–005992-10. |
| first_indexed | 2024-04-09T23:06:00Z |
| format | Article |
| id | doaj.art-1bf40945d1034d07a5ca7a9914231cc8 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-04-09T23:06:00Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-1bf40945d1034d07a5ca7a9914231cc82023-03-22T10:40:16ZengBMCBMC Nephrology1471-23692023-02-0124111110.1186/s12882-023-03072-xDesign of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney diseaseDjalila Mekahli0Max C. Liebau1Melissa A. Cadnapaphornchai2Stuart L. Goldstein3Larry A. Greenbaum4Mieczyslaw Litwin5Tomas Seeman6Franz Schaefer7Lisa M. Guay-Woodford8PKD Research Group, Department of Cellular and Molecular Medicine, KU LeuvenDepartment of Pediatrics, Center for Family Health, Center for Rare Diseases, and Center for Molecular Medicine, University Hospital Cologne and Faculty of Medicine, University of CologneRocky Mountain Pediatric Kidney Center, Rocky Mountain Hospital for Children at Presbyterian/St. Luke’s Medical CenterCenter for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of MedicineDepartment of Pediatrics, Division of Pediatric Nephrology, Emory University School of Medicine and Children’s Healthcare of AtlantaDepartment of Nephrology, Kidney Transplantation and Arterial Hypertension, Children’s Memorial Health InstituteDepartment of Pediatrics, 2nd Faculty of Medicine, Charles UniversityDivision of Pediatric Nephrology, University Children’s Hospital HeidelbergCenter for Translational Research, Children’s National Research InstituteAbstract Purpose Autosomal recessive polycystic kidney disease (ARPKD) is a hereditary condition characterized by massive kidney enlargement and developmental liver defects. Potential consequences during childhood include the need for kidney replacement therapy (KRT). We report the design of 2 ongoing clinical trials (Study 204, Study 307) to evaluate safety, tolerability, and efficacy of tolvaptan in children with ARPKD. Methods Both trials are of multinational, multicenter, open-label design. Age range at enrollment is 28 days to < 12 weeks in Study 204 and 28 days to < 18 years in Study 307. Subjects in both studies must have a clinical diagnosis of ARPKD, and those in Study 204 must additionally have signs indicative of risk of rapid progression to KRT, namely, all of: nephromegaly, multiple kidney cysts or increased kidney echogenicity suggesting microcysts, and oligohydramnios or anhydramnios. Target enrollment is 20 subjects for Study 204 and ≥ 10 subjects for Study 307. Results Follow-up is 24 months in Study 204 (with optional additional treatment up to 36 months) and 18 months in Study 307. Outcomes include safety, tolerability, change in kidney function, and percentage of subjects requiring KRT relative to historical data. Regular safety assessments monitor for possible adverse effects of treatment on parameters such as liver function, kidney function, fluid balance, electrolyte levels, and growth trajectory, with increased frequency of monitoring following tolvaptan initiation or dose escalation. Conclusions These trials will provide data on tolvaptan safety and efficacy in a population without disease-specific treatment options. Trial registration Study 204: EudraCT 2020–005991-36; Study 307: EudraCT 2020–005992-10.https://doi.org/10.1186/s12882-023-03072-xAutosomal recessive polycystic kidney disease (ARPKD)Clinical trialTolvaptanPediatricEfficacySafety |
| spellingShingle | Djalila Mekahli Max C. Liebau Melissa A. Cadnapaphornchai Stuart L. Goldstein Larry A. Greenbaum Mieczyslaw Litwin Tomas Seeman Franz Schaefer Lisa M. Guay-Woodford Design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease BMC Nephrology Autosomal recessive polycystic kidney disease (ARPKD) Clinical trial Tolvaptan Pediatric Efficacy Safety |
| title | Design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease |
| title_full | Design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease |
| title_fullStr | Design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease |
| title_full_unstemmed | Design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease |
| title_short | Design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease |
| title_sort | design of two ongoing clinical trials of tolvaptan in the treatment of pediatric patients with autosomal recessive polycystic kidney disease |
| topic | Autosomal recessive polycystic kidney disease (ARPKD) Clinical trial Tolvaptan Pediatric Efficacy Safety |
| url | https://doi.org/10.1186/s12882-023-03072-x |
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