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

Cardio-Renal Syndrome Clinical Trial

— NICHE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02343393
• Other study ID #: NICHE
• Status: Recruiting
• Phase: Phase 3
• First received: January 15, 2015
• Last updated: January 15, 2015
• Start date: January 2015
• Est. completion date: June 2016

Study information

• Verified date: January 2015
• Source: National University Hospital, Singapore
• Contact: Su Ping Carolyn Lam, MBBS, MRCP, MS
• Email: carolyn_lam[@]nuhs.edu.sg
• Is FDA regulated: No
• Health authority: Singapore: Health Sciences Authority
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. At least 21 years of age

2. Asian patients with symptomatic HF (regardless of EF) and renal impairment (eGFR<60ml/min/1.73m2)

3. At least one hospitalisation for HF during the preceeding year

4. On stable (at least 1 month) optimal medical therapy (maximum tolerated doses of ACE inhibitors or ARBs, beta blockers and aldosterone antagonists for HFREF, and optimally managed cardiovascular risk factors for HFPEF)

5. Able to complete 6 minute walk test (6MWT)

6. Able to maintain a systolic blood pressure =100mmHg

7. Able to provide written informed consent

Exclusion Criteria:

1. On chronic therapy with hydralazine and/or nitrates.

2. Known hypersensitivity to hydralazine and/or nitrates

3. Concurrent use of phosphodiesterase type 5 (PDE5) inhibitors

4. Females who are pregnant, nursing, or of childbearing potential and not practising effective contraception

5. Have had acute myocardial infarction, unstable or stable angina pectoris, or a cerebrovascular accident within the last 3 months

6. Have had cardiac revascularisation within the last 3 months or are likely to require coronary revascularisation within the study period

7. Have had cardiac arrest or life-threatening ventricular arrhythmia requiring intervention within 3 months

8. Rapidly deteriorating HF (2 admissions for acute decompensated HF, not due to non-compliance, within 6 months)

9. eGFR< 15ml/min/1.73m2, or on regular dialysis, or planned dialysis within the study period

10. Serious medical condition, emergency condition, uncontrolled systemic disease or any other medical condition that, in the judgement of the investigator, prohibits the patient from entering or potentially completing the study

11. Planned participation in any other interventional study or having received trial medication in the last 4 weeks within a clinical trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardio-Renal Syndrome
• Syndrome

Intervention

Drug:
• Hydralazine

• Isosorbide Dinitrate

Locations

Country	Name	City	State
Singapore	Changi General Hospital	Singapore
Singapore	National Heart Centre Singapore	Singapore
Singapore	National University Hospital, Singapore	Singapore

Sponsors (4)

Lead Sponsor	Collaborator
National University Hospital, Singapore	Changi General Hospital, National Heart Centre Singapore, Singapore Clinical Research Institute

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effort tolerance by assessing 6 Minute Walk Test (6MWT)		24 weeks	No
Secondary	Endothelial function as measured via a reactive hyperaemic index (RHI) by Peripheral Arterial Tonometry (PAT)		24 weeks	No
Secondary	Renal function (eGFR, Cystatin C, markers of kidney injury (proteinuria as quantified by urine protein-creatinine ratio (uPCR), NGAL))		24 weeks	No
Secondary	Cardiac structure and function by 2D and Doppler echocardiography		24 weeks	No
Secondary	Quality of Life by self-reported 36-item Short Form Health Survey (SF-36)		24 weeks	No
Secondary	Clinical outcomes by recording deaths and HF hospitalisations		24 weeks	No