Combination Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (HIDE): A Randomized, Placebo-Controlled, Pilot Trial
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Published:2020-10-15
Issue:12
Volume:1
Page:1380-1389
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ISSN:2641-7650
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Container-title:Kidney360
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language:en
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Short-container-title:Kidney360
Author:
Charytan David M.,Hsu Jesse Y.,Mc Causland Finnian R.,Waikar Sushrut S.,Ikizler T. Alp,Raj Dominic S.,Landis J. Richard,Mehrotra Rajnish,Williams Mark,DiCarli Marcelo,Skali Hicham,Kimmel Paul L.,Kliger Alan S.,Dember Laura M.,Himmelfarb Jonathan,Anderson Amanda H,Hung Adriana M,Sharma Shailendra,Weiner Daniel E., ,
Abstract
BackgroundCombination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring maintenance hemodialysis (HD) is unknown.MethodsSingle-center, randomized, placebo-controlled, double-blind pilot trial to explore safety and tolerability of ISD/HY in maintenance HD. Participants were randomized to placebo or combination ISD/HY. Dose was escalated over 3 weeks from ISD 10 mg/HY 10 mg to ISD 40 mg/HY 75 mg three times per day with the maximum tolerated dose maintained for the subsequent 21 weeks. Primary endpoints included adverse events, adverse events precluding further treatment with study medication, serious hypotension (i.e., requiring hospitalization or emergency room visit), and recurrent intra-dialytic hypotension. Efficacy signals included change in mitral annular E’ velocity by tissue Doppler echocardiography and change in left ventricular coronary flow reserve on positron emission tomography.ResultsA total of 17 individuals were randomized to ISD/HY (N=7) or placebo (N=10). All participants assigned to ISD/HY completed dose escalation to 40/75 mg, but dose reductions were required in two participants. No participants discontinued therapy. There were no serious hypotension events. Recurrent intradialytic hypotension was less frequent with ISD/HY (0.47 events/patient-year) than placebo (1.83 events/patient-year, P=0.04). In contrast, nausea (ISD/HY, 1.90 events/patient-year; placebo, 0.50 events/patient-year, P=0.03) was significantly more frequent, and headache and diarrhea were numerically but not significantly more frequent with ISD/HY. Adverse events were more frequent with ISD/HY (11.4 events/patient-year) than placebo (6.31 events/patient-year). We did not detect between-group differences in the change in E’ (P=0.34); ISD/HY showed a mean increase of 0.6 cm/s (SD 1.1), and placebo showed a mean decrease of 0.04 cm/s (SD 0.9). Changes in coronary flow reserve were minimal, −0.3 (0.2) with ISD/HY and −0.03 (0.5) in the placebo group, P=0.19.ConclusionsISD/HY appears to be well tolerated in patients being treated with maintenance HD, but headache and gastrointestinal side effects occur more frequently with ISD/HY compared with placebo.
Funder
National Institute of Diabetes and Digestive and Kidney Diseases
National Center for Advancing Translational Sciences
National Institutes of Health
Publisher
American Society of Nephrology (ASN)
Reference26 articles.
1. U.S. Renal Data System : USRDS 2018 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2018. Available at: https://www.usrds.org/media/1730/v2_c05_mortality_18_usrds.pdf. Accessed June 30, 2018
2. Nitric oxide deficiency in chronic kidney disease
3. Clinical and pathologic characteristics of dilated cardiomyopathy in hemodialysis patients
4. Increased concentration of circulating angiogenesis and nitric oxide inhibitors induces endothelial to mesenchymal transition and myocardial fibrosis in patients with chronic kidney disease
5. Myocyte/capillary mismatch in the heart of uremic patients;Amann;J Am Soc Nephrol,1998
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