Ignite Creation Date:
2025-12-25 @ 1:26 AM
Ignite Modification Date:
2026-01-21 @ 9:47 PM
Study NCT ID:
NCT02343393
Status:
UNKNOWN
Last Update Posted:
2015-01-22
First Post:
2015-01-15
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Nitrates In Combination With Hydralazine in cardiorEnal Syndrome (NICHE) Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D059347', 'term': 'Cardio-Renal Syndrome'}], 'ancestors': [{'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D006333', 'term': 'Heart Failure'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D006830', 'term': 'Hydralazine'}, {'id': 'D007548', 'term': 'Isosorbide Dinitrate'}], 'ancestors': [{'id': 'D010793', 'term': 'Phthalazines'}, {'id': 'D011724', 'term': 'Pyridazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D007547', 'term': 'Isosorbide'}, {'id': 'D013012', 'term': 'Sorbitol'}, {'id': 'D013402', 'term': 'Sugar Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 100}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2015-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-01', 'completionDateStruct': {'date': '2016-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2015-01-15', 'studyFirstSubmitDate': '2015-01-15', 'studyFirstSubmitQcDate': '2015-01-15', 'lastUpdatePostDateStruct': {'date': '2015-01-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2015-01-22', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Effort tolerance by assessing 6 Minute Walk Test (6MWT)', 'timeFrame': '24 weeks'}], 'secondaryOutcomes': [{'measure': 'Endothelial function as measured via a reactive hyperaemic index (RHI) by Peripheral Arterial Tonometry (PAT)', 'timeFrame': '24 weeks'}, {'measure': 'Renal function (eGFR, Cystatin C, markers of kidney injury (proteinuria as quantified by urine protein-creatinine ratio (uPCR), NGAL))', 'timeFrame': '24 weeks'}, {'measure': 'Cardiac structure and function by 2D and Doppler echocardiography', 'timeFrame': '24 weeks'}, {'measure': 'Quality of Life by self-reported 36-item Short Form Health Survey (SF-36)', 'timeFrame': '24 weeks'}, {'measure': 'Clinical outcomes by recording deaths and HF hospitalisations', 'timeFrame': '24 weeks'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Endothelial Dysfunction', 'Biomarkers', 'Hydralazine-Isosorbide Dinitrate'], 'conditions': ['Cardio-Renal Syndrome']}, 'descriptionModule': {'briefSummary': 'This is a single-blind, randomised, clinical trial assessing the efficacy of Hydralazine and Isosorbidedinitrate combination (oral agents) in HF patients with renal dysfunction.', 'detailedDescription': '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.\n\nEndothelial 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.\n\nIsosorbide 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.\n\nWe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. At least 21 years of age\n2. Asian patients with symptomatic HF (regardless of EF) and renal impairment (eGFR\\<60ml/min/1.73m2)\n3. At least one hospitalisation for HF during the preceeding year\n4. 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)\n5. Able to complete 6 minute walk test (6MWT)\n6. Able to maintain a systolic blood pressure ≥100mmHg\n7. Able to provide written informed consent\n\nExclusion Criteria:\n\n1. On chronic therapy with hydralazine and/or nitrates.\n2. Known hypersensitivity to hydralazine and/or nitrates\n3. Concurrent use of phosphodiesterase type 5 (PDE5) inhibitors\n4. Females who are pregnant, nursing, or of childbearing potential and not practising effective contraception\n5. Have had acute myocardial infarction, unstable or stable angina pectoris, or a cerebrovascular accident within the last 3 months\n6. Have had cardiac revascularisation within the last 3 months or are likely to require coronary revascularisation within the study period\n7. Have had cardiac arrest or life-threatening ventricular arrhythmia requiring intervention within 3 months\n8. Rapidly deteriorating HF (2 admissions for acute decompensated HF, not due to non-compliance, within 6 months)\n9. eGFR\\< 15ml/min/1.73m2, or on regular dialysis, or planned dialysis within the study period\n10. 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\n11. Planned participation in any other interventional study or having received trial medication in the last 4 weeks within a clinical trial'}, 'identificationModule': {'nctId': 'NCT02343393', 'acronym': 'NICHE', 'briefTitle': 'Nitrates In Combination With Hydralazine in cardiorEnal Syndrome (NICHE) Study', 'organization': {'class': 'OTHER', 'fullName': 'National University Hospital, Singapore'}, 'officialTitle': 'Nitrates In Combination With Hydralazine in cardiorEnal Syndrome (NICHE) Study', 'orgStudyIdInfo': {'id': 'NICHE'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'H-ISDN', 'description': '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', 'interventionNames': ['Drug: Hydralazine', 'Drug: Isosorbide Dinitrate']}, {'type': 'NO_INTERVENTION', 'label': 'Standard Medical Therapy', 'description': 'Current standard HF therapy include the use of beta-blockers, ACE inhibitors/ARBs and diuretics.'}], 'interventions': [{'name': 'Hydralazine', 'type': 'DRUG', 'armGroupLabels': ['H-ISDN']}, {'name': 'Isosorbide Dinitrate', 'type': 'DRUG', 'armGroupLabels': ['H-ISDN']}]}, 'contactsLocationsModule': {'locations': [{'zip': '119228', 'city': 'Singapore', 'status': 'RECRUITING', 'country': 'Singapore', 'contacts': [{'name': 'Shir Lynn Lim, MBBS, MRCP, MMed', 'role': 'CONTACT', 'email': 'shir_lynn_lim@nuhs.edu.sg'}, {'name': 'Shir Lynn Lim, MBBS, MRCP, MMed', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'National University Hospital, Singapore', 'geoPoint': {'lat': 1.28967, 'lon': 103.85007}}, {'zip': '169609', 'city': 'Singapore', 'status': 'NOT_YET_RECRUITING', 'country': 'Singapore', 'contacts': [{'name': 'Kheng Leng David Sim, MBBS, MRCP, MS', 'role': 'CONTACT', 'email': 'david_sim@nhcs.com.sg'}, {'name': 'Kheng Leng David Sim, MBBS, MRCP, MS', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'National Heart Centre Singapore', 'geoPoint': {'lat': 1.28967, 'lon': 103.85007}}, {'zip': '529889', 'city': 'Singapore', 'status': 'NOT_YET_RECRUITING', 'country': 'Singapore', 'contacts': [{'name': 'Kui Toh Gerard Leong, MBBS, MRCP, MS', 'role': 'CONTACT', 'email': 'gerard_leong@cgh.com.sg'}, {'name': 'Kui Toh Gerard Leong, MBBS, MRCP, MS', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Changi General Hospital', 'geoPoint': {'lat': 1.28967, 'lon': 103.85007}}], 'centralContacts': [{'name': 'Su Ping Carolyn Lam, MBBS, MRCP, MS', 'role': 'CONTACT', 'email': 'carolyn_lam@nuhs.edu.sg'}], 'overallOfficials': [{'name': 'Su Ping Carolyn Lam, MBBS, MRCP, MS', 'role': 'STUDY_CHAIR', 'affiliation': 'National University Hospital, Singapore'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National University Hospital, Singapore', 'class': 'OTHER'}, 'collaborators': [{'name': 'Singapore Clinical Research Institute', 'class': 'OTHER'}, {'name': 'Changi General Hospital', 'class': 'OTHER'}, {'name': 'National Heart Centre Singapore', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}