{"doi":"10.34067/kid.0004342020","title":"Combination Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (HIDE): A Randomized, Placebo-Controlled, Pilot Trial","abstract":"Background Combination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring maintenance hemodialysis (HD) is unknown. Methods Single-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. Results A 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. Conclusions ISD/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.","journal":"Kidney360","year":2020,"id":111309,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":337715,"name":"Jesse Y. 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DiCarli","orcid":null,"position":9,"is_corresponding":false},{"id":430886,"name":"Hicham Skali","orcid":"0000-0002-5629-4138","position":10,"is_corresponding":false},{"id":214519,"name":"Paul L. Kimmel","orcid":null,"position":11,"is_corresponding":false},{"id":528585,"name":"Alan S. Kliger","orcid":"0000-0002-9103-477X","position":12,"is_corresponding":false},{"id":277168,"name":"Laura M. Dember","orcid":"0000-0002-9735-7473","position":13,"is_corresponding":false},{"id":54241,"name":"Jonathan Himmelfarb","orcid":"0000-0002-3319-1224","position":14,"is_corresponding":false},{"id":261902,"name":"Amanda H. Anderson","orcid":"0000-0002-1454-4282","position":15,"is_corresponding":false},{"id":11400,"name":"Adriana M. Hung","orcid":"0000-0002-3203-1608","position":16,"is_corresponding":false},{"id":393837,"name":"Shailendra Sharma","orcid":null,"position":17,"is_corresponding":false},{"id":109009,"name":"Daniel E. Weiner","orcid":"0000-0002-8775-394X","position":18,"is_corresponding":false},{"id":225665,"name":"David M. Charytan","orcid":"0000-0002-7695-3583","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T23:13:05.597252Z","pmid":"35372900","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}