Clinical Trial: Nitrates In Combination With Hydralazine in cardiorEnal Syndrome (NICHE) Study

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Nitrates In Combination With Hydralazine in cardiorEnal Syndrome (NICHE) Study

Brief Summary: This is a single-blind, randomised, clinical trial assessing the efficacy of Hydralazine and Isosorbidedinitrate combination (oral agents) in HF patients with renal dysfunction.

Detailed Summary:

Cardiorenal syndrome (CRS), where renal failure and heart failure (HF) co-exist in a vicious cycle, is a very common problem of great morbidity and mortality. The management of CRS is challenging as therapeutic options are mutually contradictory and largely empirical.

Endothelial dysfunction from oxidative injury has recently emerged as a common link between the failing heart and kidneys in CRS. The endothelium plays an obligatory role in cardiovascular homeostasis, and impaired endothelium-mediated nitric oxide (NO) bioavailability is the hallmark of endothelial dysfunction. There is a high prevalence of endothelial dysfunction in our Asian HF patients, with a greater degree of dysfunction seen in those with CRS. We hypothesise that targeting endothelial dysfunction may improve clinical status among Asian patients with CRS.

Isosorbide dinitrate (ISDN) increases NO bioavailability. Concomitant hydralazine (H) therapy prevents nitrate tolerance and protects NO from oxidative stress-induced degradation. The synergistic combination of H-ISDN is thought to exert beneficial effects on the endothelium.

We aim to perform a prospective randomised controlled trial to assess the effect of H-ISDN therapy for 6 months on exercise capacity, endothelial function, renal function, clinical outcomes and quality of life (QOL) in Asian patients with CRS. Specifically, we hypothesise that H-ISDN therapy will lead to improvement in exercise capacity (6 minute walk test (6MWT)), endothelial dysfunction (assessed by non-invasive peripheral arterial tonometry(PAT)), renal function, cardiac structure and function, clinical outcomes (all-cause mortality, HF hospitalisations) and QOL in Asian patients with CRS.


Sponsor: National University Hospital, Singapore

Current Primary Outcome: Effort tolerance by assessing 6 Minute Walk Test (6MWT) [ Time Frame: 24 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Endothelial function as measured via a reactive hyperaemic index (RHI) by Peripheral Arterial Tonometry (PAT) [ Time Frame: 24 weeks ]
  • Renal function (eGFR, Cystatin C, markers of kidney injury (proteinuria as quantified by urine protein-creatinine ratio (uPCR), NGAL)) [ Time Frame: 24 weeks ]
  • Cardiac structure and function by 2D and Doppler echocardiography [ Time Frame: 24 weeks ]
  • Quality of Life by self-reported 36-item Short Form Health Survey (SF-36) [ Time Frame: 24 weeks ]
  • Clinical outcomes by recording deaths and HF hospitalisations [ Time Frame: 24 weeks ]


Original Secondary Outcome: Same as current

Information By: National University Hospital, Singapore

Dates:
Date Received: January 15, 2015
Date Started: January 2015
Date Completion: June 2016
Last Updated: January 15, 2015
Last Verified: January 2015