Cardio-Renal SyndromePhase 3NICHENCT02343393
Nitrates In Combination With Hydralazine in cardiorEnal Syndrome (NICHE) Study
A Phase 3 study testing Hydralazine and Isosorbide Dinitrate in people with Cardio-Renal Syndrome, run by National University Hospital, Singapore at 3 sites in Singapore.
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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Cardio-Renal Syndrome
- What is being tested?
- Hydralazine and Isosorbide Dinitrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesSingapore
- Study dates
- Jan 2015to Jun 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
Su Ping Carolyn Lam, MBBS, MRCP, MS contact
Singapore3 sites, 3 recruiting
- Recruiting
National University Hospital, Singapore
Singapore, 119228
Shir Lynn Lim, MBBS, MRCP, MMed, shir_lynn_lim@nuhs.edu.sg
Shir Lynn Lim, MBBS, MRCP, MMed
- Not yet recruiting
National Heart Centre Singapore
Singapore, 169609
Kheng Leng David Sim, MBBS, MRCP, MS, david_sim@nhcs.com.sg
Kheng Leng David Sim, MBBS, MRCP, MS
- Not yet recruiting
Changi General Hospital
Singapore, 529889
Kui Toh Gerard Leong, MBBS, MRCP, MS, gerard_leong@cgh.com.sg
Kui Toh Gerard Leong, MBBS, MRCP, MS
About this study
This is a single-blind, randomised, clinical trial assessing the efficacy of Hydralazine and Isosorbidedinitrate combination (oral agents) in HF patients with renal dysfunction.
Read the detailed 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.
- Conditions
- Cardio-Renal Syndrome
- Being tested
- Hydralazine, Isosorbide Dinitrate
- Keywords
- Endothelial Dysfunction, Biomarkers, Hydralazine-Isosorbide Dinitrate
- Medical subject headings
- Cardio-Renal Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydralazineDrug
Isosorbide DinitrateDrug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effort tolerance by assessing 6 Minute Walk Test (6MWT)
Measured: 24 weeks
Secondary outcomes (5)
Endothelial function as measured via a reactive hyperaemic index (RHI) by Peripheral Arterial Tonometry (PAT)
Measured: 24 weeks
Renal function (eGFR, Cystatin C, markers of kidney injury (proteinuria as quantified by urine protein-creatinine ratio (uPCR), NGAL))
Measured: 24 weeks
Cardiac structure and function by 2D and Doppler echocardiography
Measured: 24 weeks
Quality of Life by self-reported 36-item Short Form Health Survey (SF-36)
Measured: 24 weeks
Clinical outcomes by recording deaths and HF hospitalisations
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2015 (estimated)
- Study startJan 2015
- Primary completionDec 2015 (estimated)
- Study completionJun 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardio-Renal SyndromeStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Singapore Clinical Research Institute, Changi General Hospital, National Heart Centre Singapore
- Responsible party
- Sponsor
- Investigators
- Su Ping Carolyn Lam, MBBS, MRCP, MS, Study chair, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02343393
- Sponsor's protocol ID
- NICHE
- Acronym
- NICHE
- Status last verified
- Jan 2015
- First submitted
- 15 Jan 2015
- Last updated
- 22 Jan 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitrates In Combination With Hydralazine in cardiorEnal Syndrome (NICHE) Study
- ClinicalTrials.gov ID
- NCT02343393
- Acronym / sponsor ID
- NICHE / NICHE
- Conditions
- Cardio-Renal Syndrome
- Keywords
- Endothelial Dysfunction, Biomarkers, Hydralazine-Isosorbide Dinitrate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- Singapore Clinical Research Institute, Changi General Hospital, National Heart Centre Singapore
- Study start
- Jan 2015
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 22 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| H-ISDN | Experimental | Drug: Hydralazine, Drug: Isosorbide DinitrateEligible 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 |
| Standard Medical Therapy | No intervention | –Current standard HF therapy include the use of beta-blockers, ACE inhibitors/ARBs and diuretics. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydralazine | Drug | H-ISDN |
| Isosorbide Dinitrate | Drug | H-ISDN |
Primary outcome
Effort tolerance by assessing 6 Minute Walk Test (6MWT)
Time frame: 24 weeks
5 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Su Ping Carolyn Lam, MBBS, MRCP, MS contact
Su Ping Carolyn Lam, MBBS, MRCP, MS study chair
National University Hospital, Singapore
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydralazine and Isosorbide Dinitrate in people with Cardio-Renal Syndrome, run by National University Hospital, Singapore at 3 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Su Ping Carolyn Lam, MBBS, MRCP, MS (carolyn_lam@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effort tolerance by assessing 6 Minute Walk Test (6MWT) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2015.