Heart FailurePhase 1CD-NP/LVADNCT03091998
Subcu Administration of CD-NP in Heart Failure Patients With Left Ventricular Assist Device Support
A Phase 1 study testing CD-NP in people with Heart Failure and Left Ventricular Assist Device, run by Mayo Clinic.
Trial summary
The worldwide use of left ventricular assist devices (LVAD), which is mechanical device to improve hemodynamic function, has improved the outcomes of severe heart failure (HF) patients leading to the continued annual increase in the number of LVAD implantations. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Heart Failure, Left Ventricular Assist Device, Natriuretic Peptide
- What is being tested?
- CD-NP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2017to 1 May 2020
- Phase
- Phase 1
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and non-pregnant/post-menopausal/sterile females, ages 18-90, in end-stage HF with LVAD support who are stable in the healed stage at least 3 months from the LVAD implant (Destination therapy only) (the post-menopausal state is defined as the absence of menses for ≥ 1 year or serum follicle-stimulating hormone ≥ 20 IU/L; sterilization in the female is defined as bilateral tubal occlusion for ≥ 6 months, bilateral oophorectomy, or complete hysterectomy)
- Be willing to provide informed consent.
- All cardiac medications must be at stable doses 4 weeks prior to enrollment.
Who cannot join
- Known allergy or other adverse reactions to exogenous natriuretic peptides (CD-NP or its components, nesiritide, other natriuretic peptides, or related compounds).
- Women who are pregnant, or breast-feeding.
- Having received nesiritide within 7 days prior to entry into the study.
- Having received any investigational drug or device within 30 days prior to entry into the study.
- Clinically unstable patients (e.g. mean blood pressure < 70 mmHg, ongoing requirement for vasopressors, or mechanical ventilation).
- Recent hospitalization for decompensated HF or recent defibrillation for cardiac resuscitation within 30 days prior to randomization.
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- Patients with guarded prognosis who are unlikely to derive meaningful benefit from CD-NP.
- Presence of cardiac lesions or comorbidities that may contraindicate the use of natriuretic peptides, such as clinically significant cardiac valvular stenosis, hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or uncorrected congenital heart disease that contraindicates the use of vasodilators.
- Symptomatic carotid artery disease, known critical carotid stenosis, or stroke within the past 3 months
- Requirement of pressors for maintenance of blood pressure.
- Intra-aortic blood pump use.
- Severe aortic or mitral stenosis or significant LV outflow tract obstruction.
- Clinically significant renal artery stenosis > 50%
- Baseline hemoglobin < 9.0 g/dl.
- Serum sodium < 130 mEq/L, potassium < 3.6 mEq/L, or magnesium < 1.5 mEq/L.
- Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at least 5 times the upper limit of normal or bilirubin at least 5 times the upper limit of normal
- Creatinine clearance (CrCl) < 30 ml.min-1.1.73m-2, as calculated by Cockcroft-Gault formula(67) and adjusted for body surface area within 3 months or requirement for dialysis.
- Written history of alcohol or drug abuse within the past 6 months.
- Inability to communicate effectively with study personnel.
- BMI >40
About this study
Official title: A Phase I Trial to Determine Safety and Efficacy of Chronic Subcu Administration of CD-NP in Heart Failure Patients With Left Ventricular Assist Device Support
The worldwide use of left ventricular assist devices (LVAD), which is mechanical device to improve hemodynamic function, has improved the outcomes of severe heart failure (HF) patients leading to the continued annual increase in the number of LVAD implantations. However LVAD support still results in major complications such as renal failure or gastrointestinal bleeding. The investigators hypothesize that such major complications may be due to endothelial dysfunction induced by the lack of pulsatility, which may be improved by an innovative designer natriuretic peptide, CD-NP. They have demonstrated its favorable actions in animal models as well as humans, and tested its safety in LVAD patients. They hypothesize that CD-NP will have renal and endothelial protective actions through its receptor GC-A and GC-B. Thus, the investigators will test their hypothesis with a highly translational approach to examine CD-NP's role in endothelial and renal protection.
The aim is to determine safety and tolerability together with cGMP activating, neurohumoral modulating and renovascular protective properties of chronic subcutaneous delivery of CD-NP compared to placebo in stable LVAD patients for 3 days.
Read the detailed description
Stable patients with LVAD implantation (3 months s/p implantation) will undergo 3-day testing in the Mayo Clinic's Clinical Research and Trials Unit. They will undergo daily subcutaneous injection of CD-NP, or placebo, for 3 days with hemodynamic monitoring, ECHO, endothelial function assessment, and renal blood flow monitoring. Blood and urine samples will also be collected and assayed.
- Being tested
- CD-NP, Placebo
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD-NPDrug
Also called Cenderitide
Participants will receive a subcutaneous injection of CD-NP (5 mcg / kg) daily for 3 days
PlaceboOther
Also called 0.9% normal saline
Participants will receive an ~ 1mL subcutaneous injection of normal saline, in lieu of Study Drug, for 3 days
| Study group | Role | What they receive |
|---|---|---|
| Study Drug (CD-NP) | Active comparator | Participants will receive a single subcutaneous injection of CD-NP (5 ug/kg) for 3 days running Receives: Drug: CD-NP |
| Placebo (saline) | Placebo comparator | Participants will receive a single subcutaneous injection (~1 mL) of normal saline for 3 days running Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hypotension
To assess safety and tolerability (without symptomatic hypotension or mean blood pressure <70 mmHg) of chronic continuous subcutaneous infusion administration of CD-NP.
Measured: 2 weeks
Secondary outcomes (3)
Pharmacokinetic Outcome Characterization
Area under the plasma concentration versus time curve (AUC) assessed by plasma CD-NP and cGMP
Measured: 2 weeks
Renal Function
Estimated GFR from creatinine clearance and
Measured: 2 weeks
Endothelial function
Measurement by Reactive Hyperemia-peripheral arterial tonometry (RHI)
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start30 Sep 2017 (estimated)
- Primary completion1 May 2019 (estimated)
- Study completion1 May 2020 (estimated)
Why it stopped: No funding available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Injection of CD-NP vs Placebo
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tomoko Ichiki, M.D., Ph.D., Mayo Clinic
- Investigators
- Tomoko Ichiki, M.D.Ph.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03091998
- Sponsor's protocol ID
- IRB # 16-004850
- Acronym
- CD-NP/LVAD
- Status last verified
- Jul 2017
- First submitted
- 9 Mar 2017
- Last updated
- 28 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial to Determine Safety and Efficacy of Chronic Subcu Administration of CD-NP in Heart Failure Patients With Left Ventricular Assist Device Support
- ClinicalTrials.gov ID
- NCT03091998
- Acronym / sponsor ID
- CD-NP/LVAD / IRB # 16-004850
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No funding available
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 30 Sep 2017 (estimated)
- Primary completion
- 1 May 2019 (estimated)
- Study completion
- 1 May 2020 (estimated)
- First posted
- 27 Mar 2017 (actual)
- 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.
The worldwide use of left ventricular assist devices (LVAD), which is mechanical device to improve hemodynamic function, has improved the outcomes of severe heart failure (HF) patients leading to the continued annual increase in the number of LVAD implantations. However LVAD support still results in major complications such as renal failure or gastrointestinal bleeding. The investigators hypothesize that such major complications may be due to endothelial dysfunction induced by the lack of pulsatility, which may be improved by an innovative designer natriuretic peptide, CD-NP. They have demonstrated its favorable actions in animal models as well as humans, and tested its safety in LVAD patients. They hypothesize that CD-NP will have renal and endothelial protective actions through its receptor GC-A and GC-B. Thus, the investigators will test their hypothesis with a highly translational approach to examine CD-NP's role in endothelial and renal protection.
The aim is to determine safety and tolerability together with cGMP activating, neurohumoral modulating and renovascular protective properties of chronic subcutaneous delivery of CD-NP compared to placebo in stable LVAD patients for 3 days.
Detailed description
Stable patients with LVAD implantation (3 months s/p implantation) will undergo 3-day testing in the Mayo Clinic's Clinical Research and Trials Unit. They will undergo daily subcutaneous injection of CD-NP, or placebo, for 3 days with hemodynamic monitoring, ECHO, endothelial function assessment, and renal blood flow monitoring. Blood and urine samples will also be collected and assayed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Injection of CD-NP vs Placebo
| Arm | Type | Receives |
|---|---|---|
| Study Drug (CD-NP) | Active comparator | Drug: CD-NPParticipants will receive a single subcutaneous injection of CD-NP (5 ug/kg) for 3 days running |
| Placebo (saline) | Placebo comparator | Other: PlaceboParticipants will receive a single subcutaneous injection (~1 mL) of normal saline for 3 days running |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male and non-pregnant/post-menopausal/sterile females, ages 18-90, in end-stage HF with LVAD support who are stable in the healed stage at least 3 months from the LVAD implant (Destination therapy only) (the post-menopausal state is defined as the absence of menses for ≥ 1 year or serum follicle-stimulating hormone ≥ 20 IU/L; sterilization in the female is defined as bilateral tubal occlusion for ≥ 6 months, bilateral oophorectomy, or complete hysterectomy)
- Be willing to provide informed consent.
- All cardiac medications must be at stable doses 4 weeks prior to enrollment.
Key exclusion criteria (20 listed)
- Known allergy or other adverse reactions to exogenous natriuretic peptides (CD-NP or its components, nesiritide, other natriuretic peptides, or related compounds).
- Women who are pregnant, or breast-feeding.
- Having received nesiritide within 7 days prior to entry into the study.
- Having received any investigational drug or device within 30 days prior to entry into the study.
- Clinically unstable patients (e.g. mean blood pressure < 70 mmHg, ongoing requirement for vasopressors, or mechanical ventilation).
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 |
|---|---|---|
| CD-NPAlso: CenderitideParticipants will receive a subcutaneous injection of CD-NP (5 mcg / kg) daily for 3 days | Drug | Study Drug (CD-NP) |
| PlaceboAlso: 0.9% normal salineParticipants will receive an ~ 1mL subcutaneous injection of normal saline, in lieu of Study Drug, for 3 days | Other | Placebo (saline) |
Primary outcome
Hypotension
Time frame: 2 weeks
To assess safety and tolerability (without symptomatic hypotension or mean blood pressure <70 mmHg) of chronic continuous subcutaneous infusion administration of CD-NP.
3 secondary outcomes
Pharmacokinetic Outcome Characterization
Time frame: 2 weeks
Renal Function
Time frame: 2 weeks
Endothelial function
Time frame: 2 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2017.
- Individual participant dataSharing planned: No
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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.
Tomoko Ichiki, M.D.Ph.D. principal investigator
Mayo Clinic
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD-NP in people with Heart Failure and Left Ventricular Assist Device, run by Mayo Clinic.
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 3 inclusion and 20 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: withdrawn, as of the sponsor's last update on 28 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Hypotension (time frame: 2 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 28 Jul 2017.