Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis: An Analysis of the Randomized, Placebo-Controlled CaLIPSO Study. Issue 5 (8th May 2021)

• Record Type: Journal Article
• Authors: Bushinsky, David A.; Raggi, Paolo; Bover, Jordi; Ketteler, Markus; Bellasi, Antonio; Rodriguez, Mariano; Sinha, Smeeta; Garg, Rekha; Perelló, Joan; Gold, Alex; Chertow, Glenn M.
• Other Names: author non-byline.; Nash Kevin W. author non-byline.; Kaskas Marwan O. author non-byline.; Martin Edouard Rene author non-byline.; Bernardo Marializa Victorino author non-byline.; Mehta Bhasker author non-byline.; Hon George author non-byline.; Meyer Jill Marie author non-byline.; Steer Dylan Lior author non-byline.; Bhat Premila author non-byline.; Kapoian Toros author non-byline.; Sullivan James author non-byline.; Kopyt Nelson P. author non-byline.; Zeig Steven author non-byline.; Cuellar Juan Mauricio author non-byline.; Lynn Robert Isaac author non-byline.; Roer David A. author non-byline.; Gandhi Nirav Dinesh author non-byline.; Kleinman Kenneth Scott author non-byline.; Arenas Guadiz Ramon Narciso author non-byline.; Yan Jieshi author non-byline.; Seek Melvin M. author non-byline.; Durham William Tracy author non-byline.; Rakowski Daniel A. author non-byline.; Topf Joel Michels author non-byline.; Lehrner Lawrence Marshall author non-byline.; Graham Stephen Lawrence author non-byline.; Jamal Aamir Z. author non-byline.; Khawar Osman Saleem author non-byline.; Dua Sohan author non-byline.; Patak Ramachandra V. author non-byline.; Navarro Jesus Ovidio author non-byline.; Irby Braxter Pleasant author non-byline.; Joshi Sudhir Shyam author non-byline.; Darwish Riad Y author non-byline.; Anger Michael S. author non-byline.; Gandhi Kamal V. author non-byline.; Al-Saghir Fahd author non-byline.; Jim Bun author non-byline.; Singh Harmeet author non-byline.; Belart Rodríguez María Montserrat author non-byline.; Parra Emilio González author non-byline.; Planas Pons Antonio Francisco author non-byline.; Nieto Silvia Collado author non-byline.; Ibeas López José Antonio author non-byline.; Escola Joaquín Manrique author non-byline.; Marques Gonzalo Gómez author non-byline.; Díaz Gómez Joan Manuel author non-byline.; Portillo Mariano Rodríguez author non-byline.; Buades Fuster Juan Manuel author non-byline.; Terrades Natalia Ramos author non-byline.; Fernández Isabel Martínez author non-byline.; Puchades Montesa María Jesús author non-byline.; Vila Pablo Molina author non-byline.; Vilaro Meritxell Ibernón author non-byline.; Lazo Mercedes Salgueira author non-byline.; Arnal Luis Miguel Lou author non-byline.; Varela Jesús Calviño author non-byline.; Sarró Sobrín José Felipe author non-byline.; Canals Francisco Maduell author non-byline.; Sinha Smeeta author non-byline.; Mitra Sandip author non-byline.; Hutchinson Alastair author non-byline.; Eardley Kevin S. author non-byline.; Balasubramaniam Gowrie author non-byline.; Mikhail Ashraf author non-byline.; Bansal Tarun author non-byline.; author non-byline.;
• Is Part Of: Clinical journal of the American Society of Nephrology. Volume 16:Issue 5(2021)
• Page Start: 736
• Page End: 745
• Publication Date: 2021-05-08
• Subjects: bone mineral density -- matrix mineralization -- bone modeling and remodeling -- SNF472 -- cardiovascular
• DOI: 10.2215/CJN.16931020
• Languages: English
• ISSNs: 1555-9041

Abstract

Visual Abstract: Abstract : Background and objectives: In the CaLIPSO study, intravenous administration of SNF472 (300 or 600 mg) during hemodialysis significantly attenuated progression of coronary artery and aortic valve calcification. SNF472 selectively inhibits formation of hydroxyapatite, the final step in cardiovascular calcification. Because bone mineral is predominantly hydroxyapatite, we assessed changes in bone mineral density in CaLIPSO. Design, setting, participants, & measurements: Patients with coronary artery calcification at screening (Agatston score of 100–3500 U) were randomized 1:1:1 to receive placebo, 300 mg SNF472, or 600 mg SNF472 as an intravenous infusion during hemodialysis three times weekly for 52 weeks. Dual-energy x-ray absorptiometry (DXA) scans were obtained at baseline (screening) and end of treatment, and between-group changes from baseline were compared using analysis of covariance. Results: Among 274 randomized patients, 202 had evaluable DXA scans at baseline and postrandomization (the DXA-modified intention-to-treat population). Mean (95% confidence interval) changes in total-hip bone mineral density from baseline to week 52 were −1.5% (−2.7% to −0.3%), −1.5% (−2.7% to −0.4%), and −2.5% (−3.8% to −1.2%) in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. Mean (95% confidence interval) changes in femoral-neck bone mineral density from baseline to week 52 were −0.3% (−1.6% to 1.0%), −1.0% (−2.3% to 0.2%), and −2.6% (−4.0% to −1.3%), respectively. Regression analyses showed no correlation between change in coronary artery calcium volume and change in bone mineral density at either location. Changes in serum alkaline phosphatase, calcium, magnesium, phosphate, and intact parathyroid hormone levels were similar across treatment groups. Clinical fracture events were reported for four of 90, three of 92, and six of 91 patients in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. Conclusions: Bone mineral density decreased modestly in all groups over 1 year. In the 600 mg SNF472 group, the reduction appeared more pronounced. Reported fractures were infrequent in all groups. Clinical Trial registry name and registration number: Effect of SNF472 on Progression of Cardiovascular Calcification in End-Stage-Renal-Disease (ESRD) Patients on Hemodialysis (HD), NCT02966028