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

NCT02343393 | Unknown Phase 3 DMC

• 1 other identifier: NICHE
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

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.

Conditions

Cardio-Renal Syndrome

Keywords

Endothelial Dysfunction; Biomarkers; Hydralazine-Isosorbide Dinitrate

Outcome Measures

Primary Outcomes (1)

• Effort tolerance by assessing 6 Minute Walk Test (6MWT)

  24 weeks

Secondary Outcomes (5)

• Endothelial function as measured via a reactive hyperaemic index (RHI) by Peripheral Arterial Tonometry (PAT)

  24 weeks

• Renal function (eGFR, Cystatin C, markers of kidney injury (proteinuria as quantified by urine protein-creatinine ratio (uPCR), NGAL))

  24 weeks

• Cardiac structure and function by 2D and Doppler echocardiography

  24 weeks

• Quality of Life by self-reported 36-item Short Form Health Survey (SF-36)

  24 weeks

• Clinical outcomes by recording deaths and HF hospitalisations

  24 weeks

Study Arms (2)

H-ISDN

EXPERIMENTAL

Eligible patients randomised to treatment arm will be initiated on a starting dose of hydralazine 60mg and ISDN 30mg daily (20/10mg three times daily). After 7 days following the first dose, if the starting medication is well-tolerated, the patient is instructed to double the dose of study medication to the target maintenance dose of hydralazine 120mg and ISDN 60mg daily for 24 weeks

Drug: Hydralazine; Drug: Isosorbide Dinitrate

Standard Medical Therapy

NO INTERVENTION

Current standard HF therapy include the use of beta-blockers, ACE inhibitors/ARBs and diuretics.

Interventions

Hydralazine DRUG

H-ISDN

Isosorbide Dinitrate DRUG

H-ISDN

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 21 years of age
• Asian patients with symptomatic HF (regardless of EF) and renal impairment (eGFR\<60ml/min/1.73m2)
• At least one hospitalisation for HF during the preceeding year
• 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)
• Able to complete 6 minute walk test (6MWT)
• Able to maintain a systolic blood pressure ≥100mmHg
• Able to provide written informed consent

You may not qualify if:

• On chronic therapy with hydralazine and/or nitrates.
• Known hypersensitivity to hydralazine and/or nitrates
• Concurrent use of phosphodiesterase type 5 (PDE5) inhibitors
• Females who are pregnant, nursing, or of childbearing potential and not practising effective contraception
• Have had acute myocardial infarction, unstable or stable angina pectoris, or a cerebrovascular accident within the last 3 months
• Have had cardiac revascularisation within the last 3 months or are likely to require coronary revascularisation within the study period
• Have had cardiac arrest or life-threatening ventricular arrhythmia requiring intervention within 3 months
• Rapidly deteriorating HF (2 admissions for acute decompensated HF, not due to non-compliance, within 6 months)
• eGFR\< 15ml/min/1.73m2, or on regular dialysis, or planned dialysis within the study period
• 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
• Planned participation in any other interventional study or having received trial medication in the last 4 weeks within a clinical trial

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Singapore Clinical Research Institute: collaborator
• Changi General Hospital: collaborator
• National Heart Centre Singapore: collaborator

Study Sites (3)

National University Hospital, Singapore

Singapore, 119228, Singapore

RECRUITING

National Heart Centre Singapore

Singapore, 169609, Singapore

NOT YET RECRUITING

Changi General Hospital

Singapore, 529889, Singapore

NOT YET RECRUITING

MeSH Terms

Conditions

Cardio-Renal Syndrome

Interventions

Hydralazine; Isosorbide Dinitrate

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Failure; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phthalazines; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isosorbide; Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Su Ping Carolyn Lam, MBBS, MRCP, MS

  National University Hospital, Singapore

  STUDY CHAIR

Central Study Contacts

Su Ping Carolyn Lam, MBBS, MRCP, MS

CONTACT

carolyn_lam@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: January 22, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: June 1, 2016
• Last Updated: January 22, 2015

Record last verified: 2015-01

Locations

SG (3)