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Heart FailurePhase 1/2NCT02547766

Interleukin-1 Receptor Antagonist for the Treatment of Heart Failure in Patients With Left Ventricular Assist Devices

A Phase 1/2 study testing Anakinra in people with Heart Failure, run by University of Utah at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Heart failure remains a major cause of morbidity and mortality. Many patients with heart failure receive support from a left ventricular assist device (LVAD) at some point in the course of their disease. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Heart Failure
What is being tested?
Anakinra
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Apr 2015to Dec 2016
Phase
Phase 1/2
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

  • To qualify for inclusion, patients must meet the following criteria: age >18 years at date of LVAD implantation who require circulatory support with an LVAD for either a bridge-to-transplant or destination therapy indication.
  • They must also be judged by the implanting surgeon to have an expected survival to trial completion (approximately 6 months after implantation), without regard to the likelihood of cardiac transplantation.

Who cannot join

  • Exclusion criteria include the presence of a Right Ventricular Assist Device, as biventricular support is associated with decreased survival outcomes that could negatively impact the attrition rate over the course of the study.
  • Additional exclusion criteria include the inability of the patient or a trained caregiver to administer the study drug, and inability of the patient to complete the study questionnaire. - Patients with a creatinine clearance < 30 mL/min, evidence of an active infection, immunosuppression, or with an allergy to E. Coli derived products will also be excluded. -
  • Last, any patient with dependence on inflammatory modulating drugs will be excluded.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Utah

    Salt Lake City, Utah, 84132

Other trials in United States

About this study

Heart failure remains a major cause of morbidity and mortality. Many patients with heart failure receive support from a left ventricular assist device (LVAD) at some point in the course of their disease. Some of these LVAD patients experience a durable recovery after ventricular unloading with an LVAD, which may be associated with inhibition of inflammatory cytokines. This small pilot study aims to determine the biologic and clinical efficacy of an interleukin-1 receptor antagonist (Anakinra) at inducing myocardial recovery in patients supported with left ventricular assist devices.

Read the detailed description

More than 5 million Americans have heart failure, a number that is expected to increase 25% by the year 2030. Fifty percent of individuals diagnosed with heart failure die within 5 years of diagnosis. Of those patients who currently have heart failure, 5-10% have Stage D disease, requiring specialized interventions such as chronic inotropic support, mechanical circulatory support, or transplantation. Transplantation is considered curative for heart failure, but only about 2,200 heart transplants take place each year. Due to the imbalance between donors and possible recipients, a large number of patients remain who could benefit from transplantation that will never receive a heart. Many patients receive left ventricular assist devices (LVADs) to support their failing hearts, increasing their chances of survival while they wait to undergo transplantation.

It has been shown that up to 19% of patients show durable echocardiographic recovery (as measured by left ventricular ejection fraction >40%) after ventricular unloading with an LVAD. Recovery mediated by unloading with the LVAD causes several changes at the molecular level. However, the mechanisms underlying recovery at the cellular level, also known as reverse remodeling, are only recently being studied. Thus, the window of opportunity to develop adjuvant treatments to enhance recovery is just now opening.

Interestingly, patients that experience durable echocardiographic recovery have higher circulating levels of anti-inflammatory cytokines. Inhibition of inflammatory cytokines, such as with the use of receptor antagonists for inflammation-associated cytokines like Anakinra, has also been shown to reduce adverse myocardial remodeling after ischemic events and to increase exercise activity in patients with systolic heart failure. This study proposes the exogenous administration of Anakinra to end-stage heart failure patients supported with LVADs in an effort to increase both the number of patients who experience recovery and the magnitude of recovery.

While this is a small trial aimed primarily at demonstrating biologic efficacy of Anakinra, clinical efficacy in this study is also investigated. Encouraging results in this pilot study may prompt the creation of a randomized, controlled trial designed to demonstrate efficacy from a functional clinical standpoint.

Conditions
Heart Failure
Being tested
Anakinra
Keywords
Ventricular Assist Device, Recovery of Function
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AnakinraDrug

    Also called Kineret

    Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.

Study groups in NCT02547766
Study groupRoleWhat they receive
Anakinra ArmExperimentalAll patients in this arm receive Anakinra in a pre-post design. That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.
Receives: Drug: Anakinra

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Biologic Efficacy: Inflammation Marker - C-Reactive Protein

    The primary endpoint was a reduction in inflammatory markers, specifically C-reactive protein (CRP).

    Measured: 6 months post treatment

Secondary outcomes (3)

  1. Biologic Efficacy: Inflammation Marker - Neutrophil Count

    Secondary endpoints included the measure of additional inflammatory markers, including neutrophil count.

    Measured: 6 months post treatment

  2. Clinical Efficacy: Ejection Fraction

    Clinical efficacy was a secondary endpoint that was measured using ejection fraction (EF)

    Measured: 6 months post treatment

  3. Biologic Efficacy: Inflammation Marker - TNFalpha

    Secondary endpoints included the measure of additional inflammatory markers, including TNFalpha.

    Measured: 6 months post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2015 (estimated)
  2. Study startApr 2015
  3. Primary completionDec 2016
  4. Study completionDec 2016

Resources

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 1/2
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02547766
Sponsor's protocol ID
75500
Status last verified
Feb 2020
First submitted
9 Sep 2015
Last updated
17 Feb 2020
Data monitoring committee
Yes

Publications

  • Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, Banner NR, Khaghani A, Yacoub MH. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006 Nov 2;355(18):1873-84. doi: 10.1056/NEJMoa053063.

    PubMed 17079761

  • Abbate A, Van Tassell BW, Biondi-Zoccai G, Kontos MC, Grizzard JD, Spillman DW, Oddi C, Roberts CS, Melchior RD, Mueller GH, Abouzaki NA, Rengel LR, Varma A, Gambill ML, Falcao RA, Voelkel NF, Dinarello CA, Vetrovec GW. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study]. Am J Cardiol. 2013 May 15;111(10):1394-400. doi: 10.1016/j.amjcard.2013.01.287. Epub 2013 Feb 27.

    PubMed 23453459

  • Abbate A, Kontos MC, Grizzard JD, Biondi-Zoccai GG, Van Tassell BW, Robati R, Roach LM, Arena RA, Roberts CS, Varma A, Gelwix CC, Salloum FN, Hastillo A, Dinarello CA, Vetrovec GW; VCU-ART Investigators. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol. 2010 May 15;105(10):1371-1377.e1. doi: 10.1016/j.amjcard.2009.12.059. Epub 2010 Apr 2.

    PubMed 20451681

  • Drakos SG, Wever-Pinzon O, Selzman CH, Gilbert EM, Alharethi R, Reid BB, Saidi A, Diakos NA, Stoker S, Davis ES, Movsesian M, Li DY, Stehlik J, Kfoury AG; UCAR (Utah Cardiac Recovery Program) Investigators. Magnitude and time course of changes induced by continuous-flow left ventricular assist device unloading in chronic heart failure: insights into cardiac recovery. J Am Coll Cardiol. 2013 May 14;61(19):1985-94. doi: 10.1016/j.jacc.2013.01.072. Epub 2013 Mar 14.

    PubMed 23500219

  • Drakos SG, Kfoury AG, Selzman CH, Verma DR, Nanas JN, Li DY, Stehlik J. Left ventricular assist device unloading effects on myocardial structure and function: current status of the field and call for action. Curr Opin Cardiol. 2011 May;26(3):245-55. doi: 10.1097/HCO.0b013e328345af13.

    PubMed 21451407

  • Guglin M, Miller L. Myocardial recovery with left ventricular assist devices. Curr Treat Options Cardiovasc Med. 2012 Aug;14(4):370-83. doi: 10.1007/s11936-012-0190-9.

    PubMed 22760582

  • Healy AH, Bowen M, McKellar SH, Koliopoulou A, Drakos SG, Selzman CH. Interleukin-1 Receptor Antagonism as Adjunct Therapy for Heart Failure Patients with Left Ventricular Assist Devices. ASAIO J. 2021 Aug 1;67(8):e145-e147. doi: 10.1097/MAT.0000000000001347.

    PubMed 33470637

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Anakinra in people with Heart Failure, run by University of Utah 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 2 inclusion and 3 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 17 Feb 2020. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

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 17 Feb 2020). 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?

Biologic Efficacy: Inflammation Marker - C-Reactive Protein (time frame: 6 months post treatment). 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 NCT02547766, which also lists 7 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 17 Feb 2020.

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