Heart FailurePhase 2NCT01516346
Vasodilator Therapy for Heart Failure and Preserved Ejection Fraction
A Phase 2 study testing Isosorbide Dinitrate and Isosorbide Dinitrate + Hydralazine in people with Heart Failure and Congestive Heart Failure, run by Corporal Michael J. Crescenz VA Medical Center at 1 site in United States.
Trial summary
The main objective is to test the effect of prolonged therapy (24 weeks) with isosorbide dinitrate ± hydralazine on arterial wave reflections (primary endpoint). Secondary endpoints include left ventricular (LV) mass, fibrosis and diastolic function) and exercise capacity (assessed via the 6-minute walk test) in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Congestive Heart Failure
- What is being tested?
- Isosorbide Dinitrate and Isosorbide Dinitrate + Hydralazine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to 18 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Previous clinical diagnosis of heart failure with current New York Heart Association Class II-IV symptoms.
- LV ejection fraction >50% on a clinically indicated echocardiogram or ventriculogram within 12 months prior to consent, in the absence of a change in cardiovascular status, as assessed by the principal investigators.
- Must have had at least one of the following within the 12 months prior to consent
- Hospitalization for decompensated HF
- Acute treatment for HF with intravenous loop diuretic or hemofiltration.
- Chronic treatment with a loop diuretic for control of HF symptoms.
Show all 12Show fewer
- Chronic diastolic dysfunction on echocardiography as evidenced by left atrial enlargement or at least stage II diastolic dysfunction.
- Documentation of elevated NT-pro BNP levels or other natriuretic peptide marker (BNP, ANP) according to the laboratory and assay upper limit of normal in the previous year.
- Stable medical therapy as defined by:
- No addition or removal of ACE, ARB, beta-blockers, or calcium channel blockers (CCBs) for 30 days.
- No change in dosage of ACE, ARBs, beta-blockers or CCBs of more than 100% for 30 days.
- No change in diuretic dose for 10 days.
Who cannot join
- Rhythm other than sinus rhythm (i.e., atrial fibrillation).
- Neuromuscular, orthopedic or other non-cardiac condition that prevents patient from walking in a hallway.
- Non-cardiac condition limiting life expectancy to less than one year, per physician judgment.
- Current or anticipated future need for nitrate therapy.
- Valve disease (> mild aortic or mitral stenosis; > moderate aortic or mitral regurgitation).
- Hypertrophic cardiomyopathy.
Show all 23Show fewer
- Known infiltrative or inflammatory myocardial disease (amyloid, sarcoid).
- Pericardial disease.
- Primary pulmonary arteriopathy.
- Have experienced a myocardial infarction or unstable angina, or have undergone percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) within 60 days prior to consent, or requires either PTCA or CABG at the time of consent.
- Other clinically important causes of dyspnea such as morbid obesity or significant lung disease defined by clinical judgment or use of steroids or oxygen for lung disease.
- Systolic blood pressure < 110 mmHg or > 180 mm Hg.
- Diastolic blood pressure < 40 mmHg or > 100 mmHg.
- Resting heart rate (HR) > 100 bpm.
- A history of reduced ejection fraction (EF<50%).
- Severe renal dysfunction (estimated GFR <30 ml/min/1.73m2 by modified MDRD equation) GFR (mL/min/1.73 m2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African American) (conventional units), which would impede the safe administration of gadolinium for MRI studies contrast.
- Hemoglobin <10 g/dL.
- Patients with known severe liver disease (AST > 3x normal, alkaline phosphatase or bilirubin > 2x normal).
- Patients with a clinically indicated stress test demonstrating significant ischemia within a year of enrollment which was not followed by percutaneous or surgical revascularization.
- Listed for cardiac transplantation.
- Allergy to isosorbide dinitrate or hydralazine.
- Current therapy with phosphodiesterase inhibitors, such as sildenafil, vardenafil or tadalafil, since the combination of nitrates and phosphodiesterase inhibitors can result in severe hypotension.
- We will also exclude patients who are not suitable candidates for a cardiac MRI by virtue of having the following absolute or relative contraindications: (i) Central nervous system aneurysm clips; (ii) Implanted neural stimulators; (iii) Implanted cardiac pacemaker or defibrillator; (iv) Cochlear implant; (v) Ocular foreign body (e.g. metal shavings); (vi) Other implanted medical devices: (e.g. drug infusion ports); (vii) Insulin pump; (viii) Metal shrapnel or bullet; (ix) Claustrophobia; (x) Extreme obesity rendering the patient unable to fit into narrow-bore scanners; (xi) Unwillingness of the patient to undergo a cardiac MRI. All patients with metallic implants will be individually evaluated prior to MRI.
Trial locations and contacts
1 site in 1 country.
United States1 site
Philadelphia VA Medical Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: Effect of Organic Nitrates and Hydralazine on Wave Reflections and Left Ventricular Structure and Function in Heart Failure With Preserved Ejection Fraction
The main objective is to test the effect of prolonged therapy (24 weeks) with isosorbide dinitrate ± hydralazine on arterial wave reflections (primary endpoint). Secondary endpoints include left ventricular (LV) mass, fibrosis and diastolic function) and exercise capacity (assessed via the 6-minute walk test) in patients with Heart Failure and Preserved Ejection Fraction (HFPEF). We will also test the hypothesis that the reduction in arterial wave reflections induced by vasoactive therapy will correlate with the improvement in exercise capacity, LV mass, fibrosis and diastolic function. Finally, we will assess whether the hemodynamic response to an acute dose of sublingual nitroglycerin (NTG) can predict the sustained changes in the reflected wave and other hemodynamic parameters in response to chronic vasodilator therapy.
- Conditions
- Heart Failure, Congestive Heart Failure
- Being tested
- Isosorbide Dinitrate, Isosorbide Dinitrate + Hydralazine, Placebo
- Keywords
- Heart Failure, Heart failure with preserved ejection fraction (HFpEF), Vasodilators, Isosorbide dinitrate, Hydralazine, wave reflections, arterial stiffness, hemodynamics
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isosorbide DinitrateDrug
Enrolled subjects will be randomized in a blinded fashion to 1 isosorbide dinitrate capsule TID + 1 placebo capsule TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs. Subjects receiving isosorbide dinitrate will be given 20mg PO q8am, 2pm, and 8pm and will be titrated up to 40mg PO q8am, 2pm, and 8pm.
Isosorbide Dinitrate + HydralazineDrug
Enrolled subjects will be randomized in a blinded fashion to 1 isosorbide dinitrate capsule TID + 1 hydralazine capsule TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs. Subjects receiving isosorbide dinitrate will be given 20mg PO q8am, 2pm, and 8pm and will be titrated up to 40mg PO q8am, 2pm, and 8pm. Subjects receiving hydralazine will be given 37.5mg PO q8am, 2pm, and 8pm and will be titrated up to 75mg PO q8am, 2pm, and 8pm.
PlaceboDrug
Enrolled subjects will be randomized in a blinded fashion to 2 placebo capsules TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs.
| Study group | Role | What they receive |
|---|---|---|
| Isosorbide dinitrate | Active comparator | Research pharmacy-formulated capsules will be given to the subjects in two bottles. For this interventional arm, one of the bottles will contain the active ingredient Isosorbide Dinitrate and the other will contain placebo capsules.
Dosage of Isosorbide Dinitrate will be 20mg (if Stage 1) OR 40mg (if Stage 2). All the subjects will be uptitrated to Stage 2 dosing, if they tolerate Stage 1 dosing. Frequency is three times daily to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks. Receives: Drug: Isosorbide Dinitrate |
| Isosorbide dinitrate + Hydralazine | Active comparator | Research pharmacy-formulated capsules will be given to the subjects in two bottles. For this interventional arm, one of the bottles will contain the active ingredient Isosorbide Dinitrate and the other will contain the active ingredient Hydralazine.
Dosage of Isosorbide Dinitrate will be 20mg (if Stage 1) OR 40mg (if Stage 2). All the subjects will be uptitrated to Stage 2 dosing, if they tolerate Stage 1 dosing. Frequency is three times daily to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks.
Dosage of Hydralazine will be 37.5mg (if Stage 1) OR 75mg (if Stage 2). All the subjects will be uptitrated to Stage 2 dosing, if they tolerate Stage 1 dosing. Frequency is three times daily, to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks. Receives: Drug: Isosorbide Dinitrate + Hydralazine |
| Placebo | Placebo comparator | Research pharmacy-formulated capsules will be given to subjects in two bottles. For this interventional arm, both the bottles will contain placebo capsules.
Dosage will be same regardless of up-titration from Stage 1 dosing to Stage 2 dosing. Frequency is three times daily, to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wave Reflection Magnitude
The dimensionless ratio of backward (reflected) to forward wave amplitude. Higher values imply more wave reflection.
Measured: 24 weeks
Secondary outcomes (4)
LV Mass
LV mass measured by MRI, in grams normalized to height in meters raised to the 1.7 power (m^1.7)
Measured: 24 weeks
Quality of Life (Kansas City Cardiomyopathy Questionnaire Score)
Quality of life, assessed with the Kansas City cardiomyopathy questionnaire (overall summary score, which ranges from 0 to 100). Higher values imply better quality of life.
Measured: 24 weeks
Early Diastolic Mitral Annular Velocity
Diastolic mitral annular velocity measured at the basal septal mitral annulus
Measured: 24 weeks
Myocardial Extracellular Volume Fraction
Myocardial extracellular volume, expressed as percent of total tissue volume, measured by MRI (T1 mapping pre and post-gadolinium administration)
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 posted24 Jan 2012 (estimated)
- Study startJan 2012
- Primary completion5 Feb 2016
- Study completion18 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corporal Michael J. Crescenz VA Medical Center
- Sponsor type
- US federal agency
- Collaborators
- University of Pennsylvania, National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Julio A.Chirinos, Corporal Michael J. Crescenz VA Medical Center
- Investigators
- Julio A Chirinos, MD, PhD, Principal investigator, Philadelphia VA Medical Center & University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01516346
- Sponsor's protocol ID
- 01340
- Other IDs
- 5R21AG043802-02
- Status last verified
- Jun 2022
- First submitted
- 19 Jan 2012
- Last updated
- 21 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bhuiyan T, Maurer MS. Heart Failure with Preserved Ejection Fraction: Persistent Diagnosis, Therapeutic Enigma. Curr Cardiovasc Risk Rep. 2011 Oct;5(5):440-449. doi: 10.1007/s12170-011-0184-2.
PubMed 22081782Chirinos JA, Segers P. Noninvasive evaluation of left ventricular afterload: part 1: pressure and flow measurements and basic principles of wave conduction and reflection. Hypertension. 2010 Oct;56(4):555-62. doi: 10.1161/HYPERTENSIONAHA.110.157321. Epub 2010 Aug 23.
PubMed 20733089Chirinos JA, Segers P. Noninvasive evaluation of left ventricular afterload: part 2: arterial pressure-flow and pressure-volume relations in humans. Hypertension. 2010 Oct;56(4):563-70. doi: 10.1161/HYPERTENSIONAHA.110.157339. Epub 2010 Aug 23.
PubMed 20733088Endo H, Shiraishi H, Yanagisawa M. Afterload reduction by hydralazine in children with a ventricular septal defect as determined by aortic input impedance. Cardiovasc Drugs Ther. 1994 Feb;8(1):161-6. doi: 10.1007/BF00877105.
PubMed 8086327Greig LD, Leslie SJ, Gibb FW, Tan S, Newby DE, Webb DJ. Comparative effects of glyceryl trinitrate and amyl nitrite on pulse wave reflection and augmentation index. Br J Clin Pharmacol. 2005 Mar;59(3):265-70. doi: 10.1111/j.1365-2125.2004.02334.x.
PubMed 15752371Lind L, Pettersson K, Johansson K. Analysis of endothelium-dependent vasodilation by use of the radial artery pulse wave obtained by applanation tonometry. Clin Physiol Funct Imaging. 2003 Jan;23(1):50-7. doi: 10.1046/j.1475-097x.2003.00469.x.
PubMed 12558614Bradley JG, Davis KA. Orthostatic hypotension. Am Fam Physician. 2003 Dec 15;68(12):2393-8.
PubMed 14705758Downing GJ, Maulik D, Phillips C, Kadado TR. In vivo correlation of Doppler waveform analysis with arterial input impedance parameters. Ultrasound Med Biol. 1993;19(7):549-59. doi: 10.1016/0301-5629(93)90078-3.
PubMed 8310551Elkayam U, Bitar F. Effects of nitrates and hydralazine in heart failure: clinical evidence before the african american heart failure trial. Am J Cardiol. 2005 Oct 10;96(7B):37i-43i. doi: 10.1016/j.amjcard.2005.07.031. Epub 2005 Aug 9.
PubMed 16226934Brooks D, Solway S, Gibbons WJ. ATS statement on six-minute walk test. Am J Respir Crit Care Med. 2003 May 1;167(9):1287. doi: 10.1164/ajrccm.167.9.950. No abstract available.
PubMed 12714344Chirinos JA, Bhattacharya P, Kumar A, Proto E, Konda P, Segers P, Akers SR, Townsend RR, Zamani P. Impact of Diabetes Mellitus on Ventricular Structure, Arterial Stiffness, and Pulsatile Hemodynamics in Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2019 Feb 19;8(4):e011457. doi: 10.1161/JAHA.118.011457.
PubMed 30764699Zamani P, Akers S, Soto-Calderon H, Beraun M, Koppula MR, Varakantam S, Rawat D, Shiva-Kumar P, Haines PG, Chittams J, Townsend RR, Witschey WR, Segers P, Chirinos JA. Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2017 Feb 20;6(2):e004262. doi: 10.1161/JAHA.116.004262.
PubMed 28219917
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Organic Nitrates and Hydralazine on Wave Reflections and Left Ventricular Structure and Function in Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT01516346
- Acronym / sponsor ID
- 01340
- Conditions
- Heart Failure, Congestive Heart Failure
- Keywords
- Heart Failure, Heart failure with preserved ejection fraction (HFpEF), Vasodilators, Isosorbide dinitrate, Hydralazine, wave reflections, arterial stiffness, hemodynamics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Corporal Michael J. Crescenz VA Medical CenterUS federal agency
- Collaborators
- University of Pennsylvania, National Institute on Aging (NIA)
- Study start
- Jan 2012 (actual)
- Primary completion
- 5 Feb 2016 (actual)
- Study completion
- 18 Aug 2017 (actual)
- First posted
- 24 Jan 2012 (estimated)
- Results
- Posted 21 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective is to test the effect of prolonged therapy (24 weeks) with isosorbide dinitrate ± hydralazine on arterial wave reflections (primary endpoint). Secondary endpoints include left ventricular (LV) mass, fibrosis and diastolic function) and exercise capacity (assessed via the 6-minute walk test) in patients with Heart Failure and Preserved Ejection Fraction (HFPEF). We will also test the hypothesis that the reduction in arterial wave reflections induced by vasoactive therapy will correlate with the improvement in exercise capacity, LV mass, fibrosis and diastolic function. Finally, we will assess whether the hemodynamic response to an acute dose of sublingual nitroglycerin (NTG) can predict the sustained changes in the reflected wave and other hemodynamic parameters in response to chronic vasodilator therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Isosorbide dinitrate | Active comparator | Drug: Isosorbide DinitrateResearch pharmacy-formulated capsules will be given to the subjects in two bottles. For this interventional arm, one of the bottles will contain the active ingredient Isosorbide Dinitrate and the other will contain placebo capsules. Dosage of Isosorbide Dinitrate will be 20mg (if Stage 1) OR 40mg (if Stage 2). All the subjects will be uptitrated to Stage 2 dosing, if they tolerate Stage 1 dosing. Frequency is three times daily to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks. |
| Isosorbide dinitrate + Hydralazine | Active comparator | Drug: Isosorbide Dinitrate + HydralazineResearch pharmacy-formulated capsules will be given to the subjects in two bottles. For this interventional arm, one of the bottles will contain the active ingredient Isosorbide Dinitrate and the other will contain the active ingredient Hydralazine. Dosage of Isosorbide Dinitrate will be 20mg (if Stage 1) OR 40mg (if Stage 2). All the subjects will be uptitrated to Stage 2 dosing, if they tolerate Stage 1 dosing. Frequency is three times daily to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks. Dosage of Hydralazine will be 37.5mg (if Stage 1) OR 75mg (if Stage 2). All the subjects will be uptitrated to Stage 2 dosing, if they tolerate Stage 1 dosing. Frequency is three times daily, to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboResearch pharmacy-formulated capsules will be given to subjects in two bottles. For this interventional arm, both the bottles will contain placebo capsules. Dosage will be same regardless of up-titration from Stage 1 dosing to Stage 2 dosing. Frequency is three times daily, to be taken at 8 AM, 2 PM and 8 PM. Duration is for 24 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Previous clinical diagnosis of heart failure with current New York Heart Association Class II-IV symptoms.
- LV ejection fraction >50% on a clinically indicated echocardiogram or ventriculogram within 12 months prior to consent, in the absence of a change in cardiovascular status, as assessed by the principal investigators.
- Must have had at least one of the following within the 12 months prior to consent
- Stable medical therapy as defined by:
Key exclusion criteria (23 listed)
- Rhythm other than sinus rhythm (i.e., atrial fibrillation).
- Neuromuscular, orthopedic or other non-cardiac condition that prevents patient from walking in a hallway.
- Non-cardiac condition limiting life expectancy to less than one year, per physician judgment.
- Current or anticipated future need for nitrate therapy.
- Valve disease (> mild aortic or mitral stenosis; > moderate aortic or mitral regurgitation).
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 |
|---|---|---|
| Isosorbide DinitrateEnrolled subjects will be randomized in a blinded fashion to 1 isosorbide dinitrate capsule TID + 1 placebo capsule TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs. Subjects receiving isosorbide dinitrate will be given 20mg PO q8am, 2pm, and 8pm and will be titrated up to 40mg PO q8am, 2pm, and 8pm. | Drug | Isosorbide dinitrate |
| Isosorbide Dinitrate + HydralazineEnrolled subjects will be randomized in a blinded fashion to 1 isosorbide dinitrate capsule TID + 1 hydralazine capsule TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs. Subjects receiving isosorbide dinitrate will be given 20mg PO q8am, 2pm, and 8pm and will be titrated up to 40mg PO q8am, 2pm, and 8pm. Subjects receiving hydralazine will be given 37.5mg PO q8am, 2pm, and 8pm and will be titrated up to 75mg PO q8am, 2pm, and 8pm. | Drug | Isosorbide dinitrate + Hydralazine |
| PlaceboEnrolled subjects will be randomized in a blinded fashion to 2 placebo capsules TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs. | Drug | Placebo |
Primary outcome
Wave Reflection Magnitude
Time frame: 24 weeks
The dimensionless ratio of backward (reflected) to forward wave amplitude. Higher values imply more wave reflection.
4 secondary outcomes
LV Mass
Time frame: 24 weeks
Quality of Life (Kansas City Cardiomyopathy Questionnaire Score)
Time frame: 24 weeks
Early Diastolic Mitral Annular Velocity
Time frame: 24 weeks
Myocardial Extracellular Volume Fraction
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22081782Bhuiyan T, Maurer MS. Heart Failure with Preserved Ejection Fraction: Persistent Diagnosis, Therapeutic Enigma. Curr Cardiovasc Risk Rep. 2011 Oct;5(5):440-449. doi: 10.1007/s12170-011-0184-2.
- Background: PubMed 20733089Chirinos JA, Segers P. Noninvasive evaluation of left ventricular afterload: part 1: pressure and flow measurements and basic principles of wave conduction and reflection. Hypertension. 2010 Oct;56(4):555-62. doi: 10.1161/HYPERTENSIONAHA.110.157321. Epub 2010 Aug 23.
- Background: PubMed 20733088Chirinos JA, Segers P. Noninvasive evaluation of left ventricular afterload: part 2: arterial pressure-flow and pressure-volume relations in humans. Hypertension. 2010 Oct;56(4):563-70. doi: 10.1161/HYPERTENSIONAHA.110.157339. Epub 2010 Aug 23.
- Background: PubMed 8086327Endo H, Shiraishi H, Yanagisawa M. Afterload reduction by hydralazine in children with a ventricular septal defect as determined by aortic input impedance. Cardiovasc Drugs Ther. 1994 Feb;8(1):161-6. doi: 10.1007/BF00877105.
- Background: PubMed 15752371Greig LD, Leslie SJ, Gibb FW, Tan S, Newby DE, Webb DJ. Comparative effects of glyceryl trinitrate and amyl nitrite on pulse wave reflection and augmentation index. Br J Clin Pharmacol. 2005 Mar;59(3):265-70. doi: 10.1111/j.1365-2125.2004.02334.x.
- Background: PubMed 12558614Lind L, Pettersson K, Johansson K. Analysis of endothelium-dependent vasodilation by use of the radial artery pulse wave obtained by applanation tonometry. Clin Physiol Funct Imaging. 2003 Jan;23(1):50-7. doi: 10.1046/j.1475-097x.2003.00469.x.
- Background: PubMed 14705758Bradley JG, Davis KA. Orthostatic hypotension. Am Fam Physician. 2003 Dec 15;68(12):2393-8.
- Background: PubMed 8310551Downing GJ, Maulik D, Phillips C, Kadado TR. In vivo correlation of Doppler waveform analysis with arterial input impedance parameters. Ultrasound Med Biol. 1993;19(7):549-59. doi: 10.1016/0301-5629(93)90078-3.
- Background: PubMed 16226934Elkayam U, Bitar F. Effects of nitrates and hydralazine in heart failure: clinical evidence before the african american heart failure trial. Am J Cardiol. 2005 Oct 10;96(7B):37i-43i. doi: 10.1016/j.amjcard.2005.07.031. Epub 2005 Aug 9.
- Background: PubMed 12714344Brooks D, Solway S, Gibbons WJ. ATS statement on six-minute walk test. Am J Respir Crit Care Med. 2003 May 1;167(9):1287. doi: 10.1164/ajrccm.167.9.950. No abstract available.
- Derived from this study: PubMed 30764699Chirinos JA, Bhattacharya P, Kumar A, Proto E, Konda P, Segers P, Akers SR, Townsend RR, Zamani P. Impact of Diabetes Mellitus on Ventricular Structure, Arterial Stiffness, and Pulsatile Hemodynamics in Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2019 Feb 19;8(4):e011457. doi: 10.1161/JAHA.118.011457.
- Derived from this study: PubMed 28219917Zamani P, Akers S, Soto-Calderon H, Beraun M, Koppula MR, Varakantam S, Rawat D, Shiva-Kumar P, Haines PG, Chittams J, Townsend RR, Witschey WR, Segers P, Chirinos JA. Isosorbide Dinitrate, With or Without Hydralazine, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients With Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2017 Feb 20;6(2):e004262. doi: 10.1161/JAHA.116.004262.
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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.
Julio A Chirinos, MD, PhD principal investigator
Philadelphia VA Medical Center & University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isosorbide Dinitrate and Isosorbide Dinitrate + Hydralazine in people with Heart Failure and Congestive Heart Failure, run by Corporal Michael J. Crescenz VA Medical Center at 1 site in United States.
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 12 inclusion and 23 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: finished, as of the sponsor's last update on 21 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Wave Reflection Magnitude (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01516346, which also lists 12 linked publications.
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 21 Jun 2022.