NCT00328692

Brief Summary

The study is being conducted to examine whether KW-3902IV will result in greater improvement in signs and symptoms of heart failure, with less treatment failure than standard therapy, when it is added to IV loop diuretics in subjects with acute heart failure syndrome and renal impairment.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
932

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Aug 2006

Typical duration for phase_3

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 19, 2006

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 22, 2006

Completed
2 months until next milestone

Study Start

First participant enrolled

August 1, 2006

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2009

Completed
Last Updated

October 9, 2009

Status Verified

October 1, 2009

Enrollment Period

2.9 years

First QC Date

May 19, 2006

Last Update Submit

October 8, 2009

Conditions

Heart Failure, Congestive

Keywords

heart failurediureticrenal impairmentrenal function

Outcome Measures

Primary Outcomes (2)

  • effect on heart failure signs and symptoms

    3 days

  • effect on renal function

    3 days

Secondary Outcomes (2)

  • safety

    3 days

  • within trial medical costs compared to placebo

    3 days

Study Arms (2)

2

EXPERIMENTAL
Drug: rolofylline

1

PLACEBO COMPARATOR
Drug: Comparator: Placebo (unspecified)

Interventions

rolofyllineDRUG

rolofylline 30 mg IV QD; 3 days

Also known as: KW-3902IV, MK7418
2
Comparator: Placebo (unspecified)DRUG

rolofyline Pbo 30 mg IV QD; 3 days

1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • History of heart failure of at least 14 days duration for which diuretic therapy has been prescribed
  • Hospitalized for acute heart failure syndrome requiring IV diuretic therapy.
  • Impaired renal function

You may not qualify if:

  • Acute contrast induced nephropathy
  • Ongoing or planned IV therapy for heart failure with positive inotropic agents, vasopressors, vasodilators, or mechanical support with the exception of IV nitrates
  • BNP \<500pg/mL or NT-pro-BNP \<2000 pg/mL
  • Ongoing or planned treatment with ultrafiltration, hemofiltration, or dialysis
  • Severe pulmonary disease
  • Significant stenotic valvular disease
  • Heart transplant recipient or admitted for cardiac transplantation
  • Clinical evidence of acute coronary syndrome in the 2 weeks prior to screening
  • Heart failure due to significant arrhythmias
  • Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy.
  • Known hepatic impairment
  • Non-cardiac pulmonary edema, including suspected sepsis
  • Allergy to soybean oil or eggs
  • History of seizure
  • Stroke within 2 years
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (11)

  • Metra M, Cotter G, Senger S, Edwards C, Cleland JG, Ponikowski P, Cursack GC, Milo O, Teerlink JR, Givertz MM, O'Connor CM, Dittrich HC, Bloomfield DM, Voors AA, Davison BA. Prognostic Significance of Creatinine Increases During an Acute Heart Failure Admission in Patients With and Without Residual Congestion: A Post Hoc Analysis of the PROTECT Data. Circ Heart Fail. 2018 May;11(5):e004644. doi: 10.1161/CIRCHEARTFAILURE.117.004644.

    PMID: 29748350DERIVED

  • Tromp J, Khan MAF, Mentz RJ, O'Connor CM, Metra M, Dittrich HC, Ponikowski P, Teerlink JR, Cotter G, Davison B, Cleland JGF, Givertz MM, Bloomfield DM, Van Veldhuisen DJ, Hillege HL, Voors AA, van der Meer P. Biomarker Profiles of Acute Heart Failure Patients With a Mid-Range Ejection Fraction. JACC Heart Fail. 2017 Jul;5(7):507-517. doi: 10.1016/j.jchf.2017.04.007. Epub 2017 Jun 14.

    PMID: 28624483DERIVED

  • Matsue Y, van der Meer P, Damman K, Metra M, O'Connor CM, Ponikowski P, Teerlink JR, Cotter G, Davison B, Cleland JG, Givertz MM, Bloomfield DM, Dittrich HC, Gansevoort RT, Bakker SJ, van der Harst P, Hillege HL, van Veldhuisen DJ, Voors AA. Blood urea nitrogen-to-creatinine ratio in the general population and in patients with acute heart failure. Heart. 2017 Mar;103(6):407-413. doi: 10.1136/heartjnl-2016-310112. Epub 2016 Sep 22.

    PMID: 27658757DERIVED

  • Tromp J, Meyer S, Mentz RJ, O'Connor CM, Metra M, Dittrich HC, Ponikowski P, Teerlink JR, Cotter G, Davison B, Cleland JG, Givertz MM, Bloomfield DM, van Veldhuisen DJ, Hillege HL, Voors AA, van der Meer P. Acute heart failure in the young: Clinical characteristics and biomarker profiles. Int J Cardiol. 2016 Oct 15;221:1067-72. doi: 10.1016/j.ijcard.2016.06.339. Epub 2016 Jul 5.

    PMID: 27448534DERIVED

  • Givertz MM, Postmus D, Hillege HL, Mansoor GA, Massie BM, Davison BA, Ponikowski P, Metra M, Teerlink JR, Cleland JG, Dittrich HC, O'Connor CM, Cotter G, Voors AA. Renal function trajectories and clinical outcomes in acute heart failure. Circ Heart Fail. 2014 Jan;7(1):59-67. doi: 10.1161/CIRCHEARTFAILURE.113.000556. Epub 2013 Nov 26.

    PMID: 24281137DERIVED

  • Cleland JG, Chiswell K, Teerlink JR, Stevens S, Fiuzat M, Givertz MM, Davison BA, Mansoor GA, Ponikowski P, Voors AA, Cotter G, Metra M, Massie BM, O'Connor CM. Predictors of postdischarge outcomes from information acquired shortly after admission for acute heart failure: a report from the Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) Study. Circ Heart Fail. 2014 Jan;7(1):76-87. doi: 10.1161/CIRCHEARTFAILURE.113.000284. Epub 2013 Nov 26.

    PMID: 24281134DERIVED

  • Teerlink JR, Iragui VJ, Mohr JP, Carson PE, Hauptman PJ, Lovett DH, Miller AB, Pina IL, Thomson S, Varosy PD, Zile MR, Cleland JG, Givertz MM, Metra M, Ponikowski P, Voors AA, Davison BA, Cotter G, Wolko D, Delucca P, Salerno CM, Mansoor GA, Dittrich H, O'Connor CM, Massie BM. The safety of an adenosine A(1)-receptor antagonist, rolofylline, in patients with acute heart failure and renal impairment: findings from PROTECT. Drug Saf. 2012 Mar 1;35(3):233-44. doi: 10.2165/11594680-000000000-00000.

    PMID: 22339573DERIVED

  • O'Connor CM, Fiuzat M, Lombardi C, Fujita K, Jia G, Davison BA, Cleland J, Bloomfield D, Dittrich HC, Delucca P, Givertz MM, Mansoor G, Ponikowski P, Teerlink JR, Voors AA, Massie BM, Cotter G, Metra M. Impact of serial troponin release on outcomes in patients with acute heart failure: analysis from the PROTECT pilot study. Circ Heart Fail. 2011 Nov;4(6):724-32. doi: 10.1161/CIRCHEARTFAILURE.111.961581. Epub 2011 Sep 6.

    PMID: 21900185DERIVED

  • Voors AA, Dittrich HC, Massie BM, DeLucca P, Mansoor GA, Metra M, Cotter G, Weatherley BD, Ponikowski P, Teerlink JR, Cleland JG, O'Connor CM, Givertz MM. Effects of the adenosine A1 receptor antagonist rolofylline on renal function in patients with acute heart failure and renal dysfunction: results from PROTECT (Placebo-Controlled Randomized Study of the Selective Adenosine A1 Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). J Am Coll Cardiol. 2011 May 10;57(19):1899-907. doi: 10.1016/j.jacc.2010.11.057.

    PMID: 21545947DERIVED

  • Massie BM, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Weatherley BD, Cleland JG, Givertz MM, Voors A, DeLucca P, Mansoor GA, Salerno CM, Bloomfield DM, Dittrich HC; PROTECT Investigators and Committees. Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. N Engl J Med. 2010 Oct 7;363(15):1419-28. doi: 10.1056/NEJMoa0912613.

    PMID: 20925544DERIVED

  • Cotter G, Dittrich HC, Weatherley BD, Bloomfield DM, O'Connor CM, Metra M, Massie BM; Protect Steering Committee, Investigators, and Coordinators. The PROTECT pilot study: a randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist rolofylline in patients with acute heart failure and renal impairment. J Card Fail. 2008 Oct;14(8):631-40. doi: 10.1016/j.cardfail.2008.08.010. Epub 2008 Sep 14.

    PMID: 18926433DERIVED

MeSH Terms

Conditions

Heart FailureRenal Insufficiency

Interventions

rolofylline

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Study Officials

  • Barry Massie, MD

    University of California San Francisco, USA

    STUDY CHAIR

  • Christopher O'Connor, MD

    Duke University, USA

    STUDY CHAIR

  • Marco Metra, MD

    University of Brescia, Italy

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

May 19, 2006

First Posted

May 22, 2006

Study Start

August 1, 2006

Primary Completion

July 1, 2009

Study Completion

July 1, 2009

Last Updated

October 9, 2009

Record last verified: 2009-10