Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments
Background Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release fo...
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| Veröffentlicht in: | Pediatric nephrology (Berlin, West) West), 2021-01, Vol.36 (1), p.83-91 |
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| creator | Bertholet-Thomas, Aurélia Guittet, Catherine Manso-Silván, Maria A. Castang, Arnaud Baudouin, Véronique Cailliez, Mathilde Di Maio, Massimo Gillion-Boyer, Olivia Golubovic, Emilija Harambat, Jérôme Klein, Alexandre Knebelmann, Bertrand Nobili, François Novo, Robert Podracka, Ludmila Roussey-Kesler, Gwenaëlle Stylianou, Christos Granier, Luc-André |
| description | Background
Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release formulation, ADV7103, has been developed to achieve a sustained effect with an improved dosing scheme.
Methods
In a multicenter, open-label, non-inferiority trial (
n
= 37), patients with dRTA were switched from SoC to ADV7103. Mean plasma bicarbonate values and proportion of responders during steady state therapy with both treatments were compared, as were other blood and urine parameters, as well as acceptability, tolerability, and safety.
Results
When switching from SoC to ADV7103, the number of daily intakes was reduced from a median of three to twice daily. Mean plasma bicarbonate was increased and non-inferiority of ADV7103 was demonstrated (
p
|
| doi_str_mv | 10.1007/s00467-020-04693-2 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7701073</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A650474837</galeid><sourcerecordid>A650474837</sourcerecordid><originalsourceid>FETCH-LOGICAL-c644t-31514600097868f81c3fc6bba73967a1bd65c2373e3e9c9a30398974388aad0f3</originalsourceid><addsrcrecordid>eNp9ksFu1DAQhiMEoqXwAhyQJSQEhxQ7zsZJD0irqlCkSlxA6s2aOJNdV157sZNF-2o8HRO2tN1qhSIltuebf8aTP8teC34qOFcfE-dlpXJe8JwWjcyLJ9mxKGWRi6a-fpod80YKConro-xFSjec83pWV8-zI1koUahKHGe_L_reGjBbBr5jCXoctiz0tGPW-7CBwW6QrWNwwS-wyyM6hITMhFVrPUWDZ10cF0SzNW3RD4n9ssOSdTYN4FhET-9hbEcHkYGxXUg2nU0Fwhp97qBFN8mtIe6KDdFSxgZjGhMjDd9B7KaeDMQpijCspjIvs2c9uISvbr8n2Y_PF9_PL_Orb1--ns-vclOV5ZBLMRNlRXdvVF3VfS2M7E3VtqBkUykQbVfNTCGVRImNaUBy2dSNKmVdA3S8lyfZp53uemxX2BmqHcHpdbQriFsdwOr9iLdLvQgbrRQXXEkS-LATWD5Ku5xf6emMU4-latRGEPv-tlgMP0dMg17ZZNA58BjGpIuyULNixsua0LeP0JswRpr2RFFZIatidk8twKG2vg_Uo5lE9bwiHUVKiqj8ALVAj3Sh4LG3dLzHnx7g6elwZc3BhHcPEpYIblim4MbJQGkfLHagiSGliP3dxATXk-31zvaabK__2l4XlPTm4S-6S_nncwLkDkgUIiPH-1n9R_YPTr0Ojw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2473313625</pqid></control><display><type>article</type><title>Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Bertholet-Thomas, Aurélia ; Guittet, Catherine ; Manso-Silván, Maria A. ; Castang, Arnaud ; Baudouin, Véronique ; Cailliez, Mathilde ; Di Maio, Massimo ; Gillion-Boyer, Olivia ; Golubovic, Emilija ; Harambat, Jérôme ; Klein, Alexandre ; Knebelmann, Bertrand ; Nobili, François ; Novo, Robert ; Podracka, Ludmila ; Roussey-Kesler, Gwenaëlle ; Stylianou, Christos ; Granier, Luc-André</creator><creatorcontrib>Bertholet-Thomas, Aurélia ; Guittet, Catherine ; Manso-Silván, Maria A. ; Castang, Arnaud ; Baudouin, Véronique ; Cailliez, Mathilde ; Di Maio, Massimo ; Gillion-Boyer, Olivia ; Golubovic, Emilija ; Harambat, Jérôme ; Klein, Alexandre ; Knebelmann, Bertrand ; Nobili, François ; Novo, Robert ; Podracka, Ludmila ; Roussey-Kesler, Gwenaëlle ; Stylianou, Christos ; Granier, Luc-André</creatorcontrib><description>Background
Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release formulation, ADV7103, has been developed to achieve a sustained effect with an improved dosing scheme.
Methods
In a multicenter, open-label, non-inferiority trial (
n
= 37), patients with dRTA were switched from SoC to ADV7103. Mean plasma bicarbonate values and proportion of responders during steady state therapy with both treatments were compared, as were other blood and urine parameters, as well as acceptability, tolerability, and safety.
Results
When switching from SoC to ADV7103, the number of daily intakes was reduced from a median of three to twice daily. Mean plasma bicarbonate was increased and non-inferiority of ADV7103 was demonstrated (
p
< 0.0001, per protocol), as was statistical superiority (
p
= 0.0008, intention to treat [ITT]), and the response rate increased from 43 to 90% with ADV7103 (
p
< 0.001, ITT). Urine calcium/citrate ratio was reduced below the threshold for risk of lithogenesis with ADV7103 in 56% of previously non-responders with SoC (
p
= 0.021, ITT). Palatability was improved (difference [95% CI] of 25 [10.7, 39.2] mm) and gastrointestinal discomfort was reduced (difference [95% CI] of − 14.2 [− 25.9, − 2.6] mm) with ADV7103.
Conclusions
Plasma bicarbonate levels and response rate were significantly higher with ADV7103 than with SoC. Urine calcium/citrate ratio, palatability, and gastrointestinal safety were significantly improved, supporting the use of ADV7103 as first-line treatment for dRTA.
Trial registration
Registered as EudraCT 2013-002988-25 on the 1st July 2013
Graphical abstract</description><identifier>ISSN: 0931-041X</identifier><identifier>EISSN: 1432-198X</identifier><identifier>DOI: 10.1007/s00467-020-04693-2</identifier><identifier>PMID: 32712761</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Acidosis ; Acidosis, Renal Tubular - drug therapy ; Bicarbonates ; Calcium ; Citrates ; Citric acid ; Controlled release ; Controlled release preparations ; Drug therapy ; Drug therapy, Combination ; Drugs ; Human health and pathology ; Humans ; Life Sciences ; Medicine ; Medicine & Public Health ; Nephrology ; Original ; Original Article ; Palatability ; Pediatric research ; Pediatrics ; Pharmaceutical Preparations ; Pharmaceutical sciences ; Pharmacology ; Plasma ; Renal tubular acidosis ; Safety ; Santé publique et épidémiologie ; Standard of Care ; Testing ; Urine ; Urology ; Urology and Nephrology</subject><ispartof>Pediatric nephrology (Berlin, West), 2021-01, Vol.36 (1), p.83-91</ispartof><rights>The Author(s) 2020</rights><rights>COPYRIGHT 2021 Springer</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c644t-31514600097868f81c3fc6bba73967a1bd65c2373e3e9c9a30398974388aad0f3</citedby><cites>FETCH-LOGICAL-c644t-31514600097868f81c3fc6bba73967a1bd65c2373e3e9c9a30398974388aad0f3</cites><orcidid>0000-0002-4207-824X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00467-020-04693-2$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00467-020-04693-2$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32712761$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03154797$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bertholet-Thomas, Aurélia</creatorcontrib><creatorcontrib>Guittet, Catherine</creatorcontrib><creatorcontrib>Manso-Silván, Maria A.</creatorcontrib><creatorcontrib>Castang, Arnaud</creatorcontrib><creatorcontrib>Baudouin, Véronique</creatorcontrib><creatorcontrib>Cailliez, Mathilde</creatorcontrib><creatorcontrib>Di Maio, Massimo</creatorcontrib><creatorcontrib>Gillion-Boyer, Olivia</creatorcontrib><creatorcontrib>Golubovic, Emilija</creatorcontrib><creatorcontrib>Harambat, Jérôme</creatorcontrib><creatorcontrib>Klein, Alexandre</creatorcontrib><creatorcontrib>Knebelmann, Bertrand</creatorcontrib><creatorcontrib>Nobili, François</creatorcontrib><creatorcontrib>Novo, Robert</creatorcontrib><creatorcontrib>Podracka, Ludmila</creatorcontrib><creatorcontrib>Roussey-Kesler, Gwenaëlle</creatorcontrib><creatorcontrib>Stylianou, Christos</creatorcontrib><creatorcontrib>Granier, Luc-André</creatorcontrib><title>Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments</title><title>Pediatric nephrology (Berlin, West)</title><addtitle>Pediatr Nephrol</addtitle><addtitle>Pediatr Nephrol</addtitle><description>Background
Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release formulation, ADV7103, has been developed to achieve a sustained effect with an improved dosing scheme.
Methods
In a multicenter, open-label, non-inferiority trial (
n
= 37), patients with dRTA were switched from SoC to ADV7103. Mean plasma bicarbonate values and proportion of responders during steady state therapy with both treatments were compared, as were other blood and urine parameters, as well as acceptability, tolerability, and safety.
Results
When switching from SoC to ADV7103, the number of daily intakes was reduced from a median of three to twice daily. Mean plasma bicarbonate was increased and non-inferiority of ADV7103 was demonstrated (
p
< 0.0001, per protocol), as was statistical superiority (
p
= 0.0008, intention to treat [ITT]), and the response rate increased from 43 to 90% with ADV7103 (
p
< 0.001, ITT). Urine calcium/citrate ratio was reduced below the threshold for risk of lithogenesis with ADV7103 in 56% of previously non-responders with SoC (
p
= 0.021, ITT). Palatability was improved (difference [95% CI] of 25 [10.7, 39.2] mm) and gastrointestinal discomfort was reduced (difference [95% CI] of − 14.2 [− 25.9, − 2.6] mm) with ADV7103.
Conclusions
Plasma bicarbonate levels and response rate were significantly higher with ADV7103 than with SoC. Urine calcium/citrate ratio, palatability, and gastrointestinal safety were significantly improved, supporting the use of ADV7103 as first-line treatment for dRTA.
Trial registration
Registered as EudraCT 2013-002988-25 on the 1st July 2013
Graphical abstract</description><subject>Acidosis</subject><subject>Acidosis, Renal Tubular - drug therapy</subject><subject>Bicarbonates</subject><subject>Calcium</subject><subject>Citrates</subject><subject>Citric acid</subject><subject>Controlled release</subject><subject>Controlled release preparations</subject><subject>Drug therapy</subject><subject>Drug therapy, Combination</subject><subject>Drugs</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Nephrology</subject><subject>Original</subject><subject>Original Article</subject><subject>Palatability</subject><subject>Pediatric research</subject><subject>Pediatrics</subject><subject>Pharmaceutical Preparations</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacology</subject><subject>Plasma</subject><subject>Renal tubular acidosis</subject><subject>Safety</subject><subject>Santé publique et épidémiologie</subject><subject>Standard of Care</subject><subject>Testing</subject><subject>Urine</subject><subject>Urology</subject><subject>Urology and Nephrology</subject><issn>0931-041X</issn><issn>1432-198X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9ksFu1DAQhiMEoqXwAhyQJSQEhxQ7zsZJD0irqlCkSlxA6s2aOJNdV157sZNF-2o8HRO2tN1qhSIltuebf8aTP8teC34qOFcfE-dlpXJe8JwWjcyLJ9mxKGWRi6a-fpod80YKConro-xFSjec83pWV8-zI1koUahKHGe_L_reGjBbBr5jCXoctiz0tGPW-7CBwW6QrWNwwS-wyyM6hITMhFVrPUWDZ10cF0SzNW3RD4n9ssOSdTYN4FhET-9hbEcHkYGxXUg2nU0Fwhp97qBFN8mtIe6KDdFSxgZjGhMjDd9B7KaeDMQpijCspjIvs2c9uISvbr8n2Y_PF9_PL_Orb1--ns-vclOV5ZBLMRNlRXdvVF3VfS2M7E3VtqBkUykQbVfNTCGVRImNaUBy2dSNKmVdA3S8lyfZp53uemxX2BmqHcHpdbQriFsdwOr9iLdLvQgbrRQXXEkS-LATWD5Ku5xf6emMU4-latRGEPv-tlgMP0dMg17ZZNA58BjGpIuyULNixsua0LeP0JswRpr2RFFZIatidk8twKG2vg_Uo5lE9bwiHUVKiqj8ALVAj3Sh4LG3dLzHnx7g6elwZc3BhHcPEpYIblim4MbJQGkfLHagiSGliP3dxATXk-31zvaabK__2l4XlPTm4S-6S_nncwLkDkgUIiPH-1n9R_YPTr0Ojw</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Bertholet-Thomas, Aurélia</creator><creator>Guittet, Catherine</creator><creator>Manso-Silván, Maria A.</creator><creator>Castang, Arnaud</creator><creator>Baudouin, Véronique</creator><creator>Cailliez, Mathilde</creator><creator>Di Maio, Massimo</creator><creator>Gillion-Boyer, Olivia</creator><creator>Golubovic, Emilija</creator><creator>Harambat, Jérôme</creator><creator>Klein, Alexandre</creator><creator>Knebelmann, Bertrand</creator><creator>Nobili, François</creator><creator>Novo, Robert</creator><creator>Podracka, Ludmila</creator><creator>Roussey-Kesler, Gwenaëlle</creator><creator>Stylianou, Christos</creator><creator>Granier, Luc-André</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><general>Springer Verlag</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4207-824X</orcidid></search><sort><creationdate>20210101</creationdate><title>Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments</title><author>Bertholet-Thomas, Aurélia ; Guittet, Catherine ; Manso-Silván, Maria A. ; Castang, Arnaud ; Baudouin, Véronique ; Cailliez, Mathilde ; Di Maio, Massimo ; Gillion-Boyer, Olivia ; Golubovic, Emilija ; Harambat, Jérôme ; Klein, Alexandre ; Knebelmann, Bertrand ; Nobili, François ; Novo, Robert ; Podracka, Ludmila ; Roussey-Kesler, Gwenaëlle ; Stylianou, Christos ; Granier, Luc-André</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c644t-31514600097868f81c3fc6bba73967a1bd65c2373e3e9c9a30398974388aad0f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acidosis</topic><topic>Acidosis, Renal Tubular - drug therapy</topic><topic>Bicarbonates</topic><topic>Calcium</topic><topic>Citrates</topic><topic>Citric acid</topic><topic>Controlled release</topic><topic>Controlled release preparations</topic><topic>Drug therapy</topic><topic>Drug therapy, Combination</topic><topic>Drugs</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Nephrology</topic><topic>Original</topic><topic>Original Article</topic><topic>Palatability</topic><topic>Pediatric research</topic><topic>Pediatrics</topic><topic>Pharmaceutical Preparations</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacology</topic><topic>Plasma</topic><topic>Renal tubular acidosis</topic><topic>Safety</topic><topic>Santé publique et épidémiologie</topic><topic>Standard of Care</topic><topic>Testing</topic><topic>Urine</topic><topic>Urology</topic><topic>Urology and Nephrology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bertholet-Thomas, Aurélia</creatorcontrib><creatorcontrib>Guittet, Catherine</creatorcontrib><creatorcontrib>Manso-Silván, Maria A.</creatorcontrib><creatorcontrib>Castang, Arnaud</creatorcontrib><creatorcontrib>Baudouin, Véronique</creatorcontrib><creatorcontrib>Cailliez, Mathilde</creatorcontrib><creatorcontrib>Di Maio, Massimo</creatorcontrib><creatorcontrib>Gillion-Boyer, Olivia</creatorcontrib><creatorcontrib>Golubovic, Emilija</creatorcontrib><creatorcontrib>Harambat, Jérôme</creatorcontrib><creatorcontrib>Klein, Alexandre</creatorcontrib><creatorcontrib>Knebelmann, Bertrand</creatorcontrib><creatorcontrib>Nobili, François</creatorcontrib><creatorcontrib>Novo, Robert</creatorcontrib><creatorcontrib>Podracka, Ludmila</creatorcontrib><creatorcontrib>Roussey-Kesler, Gwenaëlle</creatorcontrib><creatorcontrib>Stylianou, Christos</creatorcontrib><creatorcontrib>Granier, Luc-André</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pediatric nephrology (Berlin, West)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bertholet-Thomas, Aurélia</au><au>Guittet, Catherine</au><au>Manso-Silván, Maria A.</au><au>Castang, Arnaud</au><au>Baudouin, Véronique</au><au>Cailliez, Mathilde</au><au>Di Maio, Massimo</au><au>Gillion-Boyer, Olivia</au><au>Golubovic, Emilija</au><au>Harambat, Jérôme</au><au>Klein, Alexandre</au><au>Knebelmann, Bertrand</au><au>Nobili, François</au><au>Novo, Robert</au><au>Podracka, Ludmila</au><au>Roussey-Kesler, Gwenaëlle</au><au>Stylianou, Christos</au><au>Granier, Luc-André</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments</atitle><jtitle>Pediatric nephrology (Berlin, West)</jtitle><stitle>Pediatr Nephrol</stitle><addtitle>Pediatr Nephrol</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>36</volume><issue>1</issue><spage>83</spage><epage>91</epage><pages>83-91</pages><issn>0931-041X</issn><eissn>1432-198X</eissn><abstract>Background
Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release formulation, ADV7103, has been developed to achieve a sustained effect with an improved dosing scheme.
Methods
In a multicenter, open-label, non-inferiority trial (
n
= 37), patients with dRTA were switched from SoC to ADV7103. Mean plasma bicarbonate values and proportion of responders during steady state therapy with both treatments were compared, as were other blood and urine parameters, as well as acceptability, tolerability, and safety.
Results
When switching from SoC to ADV7103, the number of daily intakes was reduced from a median of three to twice daily. Mean plasma bicarbonate was increased and non-inferiority of ADV7103 was demonstrated (
p
< 0.0001, per protocol), as was statistical superiority (
p
= 0.0008, intention to treat [ITT]), and the response rate increased from 43 to 90% with ADV7103 (
p
< 0.001, ITT). Urine calcium/citrate ratio was reduced below the threshold for risk of lithogenesis with ADV7103 in 56% of previously non-responders with SoC (
p
= 0.021, ITT). Palatability was improved (difference [95% CI] of 25 [10.7, 39.2] mm) and gastrointestinal discomfort was reduced (difference [95% CI] of − 14.2 [− 25.9, − 2.6] mm) with ADV7103.
Conclusions
Plasma bicarbonate levels and response rate were significantly higher with ADV7103 than with SoC. Urine calcium/citrate ratio, palatability, and gastrointestinal safety were significantly improved, supporting the use of ADV7103 as first-line treatment for dRTA.
Trial registration
Registered as EudraCT 2013-002988-25 on the 1st July 2013
Graphical abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32712761</pmid><doi>10.1007/s00467-020-04693-2</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-4207-824X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0931-041X |
| ispartof | Pediatric nephrology (Berlin, West), 2021-01, Vol.36 (1), p.83-91 |
| issn | 0931-041X 1432-198X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7701073 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Acidosis Acidosis, Renal Tubular - drug therapy Bicarbonates Calcium Citrates Citric acid Controlled release Controlled release preparations Drug therapy Drug therapy, Combination Drugs Human health and pathology Humans Life Sciences Medicine Medicine & Public Health Nephrology Original Original Article Palatability Pediatric research Pediatrics Pharmaceutical Preparations Pharmaceutical sciences Pharmacology Plasma Renal tubular acidosis Safety Santé publique et épidémiologie Standard of Care Testing Urine Urology Urology and Nephrology |
| title | Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T00%3A10%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20and%20safety%20of%20an%20innovative%20prolonged-release%20combination%20drug%20in%20patients%20with%20distal%20renal%20tubular%20acidosis:%20an%20open-label%20comparative%20trial%20versus%20standard%20of%20care%20treatments&rft.jtitle=Pediatric%20nephrology%20(Berlin,%20West)&rft.au=Bertholet-Thomas,%20Aur%C3%A9lia&rft.date=2021-01-01&rft.volume=36&rft.issue=1&rft.spage=83&rft.epage=91&rft.pages=83-91&rft.issn=0931-041X&rft.eissn=1432-198X&rft_id=info:doi/10.1007/s00467-020-04693-2&rft_dat=%3Cgale_pubme%3EA650474837%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2473313625&rft_id=info:pmid/32712761&rft_galeid=A650474837&rfr_iscdi=true |