Clinical trial NCT00744341: Safety and Efficacy Study to Evaluate the Effect of SLV320 on Renal Function in Patients With Worsening Heart Failure
Official title: A Double-Blind, Placebo-Controlled, Randomized, Multi-Center, Dose-Finding Study of SLV320, a Selective A1 Adenosine Receptor Antagonist, to Evaluate the Effect on Renal Function and Safety in Subjects Hospitalized With Acute Decompensated Heart Failure and Renal Dysfunction (Reno-Defend 1)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Decompensated Heart Failure; Renal Dysfunction
Keywords: SLV320; Acute Decompensated Heart Failure (ADHF); chronic heart failure; renal failure; I.V. doses; hospitalization
Lead sponsor: Solvay Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-08-29
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy and safety of IV SLV320 in acute heart failure patients with renal dysfunction.

Detailed description: The purpose of this study is to determine the efficacy and safety of IV SLV320 in acute heart failure patients with renal dysfunction.

Eligibility criteria: Inclusion Criteria Renal dysfunction defined as estimated eGFR of 20-80 mL/min; history of systolic or diastolic chronic heart failure of at least 14 days duration for which loop diuretic therapy has been prescribed; clinical evidence for volume overload; BNP ≥ 500 pg/mL or NT-pro-BNP \> 2000 pg/mL; hospitalization.

Exclusion Criteria Have low output syndrome, defined as having the need for treatment with I.V. inotropes or vasopressors; Need mechanical ventilation; Have significant stenotic valvular disease (severe aortic or mitral stenosis); Have myocardial infarction or hemodynamically destabilizing significant arrythmias (ventricular tachycardia, bradyarrythmias with slow ventricular rate \[\<45 bpm\] or atrial fibrillation/flutter with a rapid ventricular response of \>120 bpm), or electrocardiographic evidence of 2nd degree heart block (Mobitz Type II) or 3rd degree AV-block in the absence of a pacemaker, within 30 days of screening; Have acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy

Primary outcomes:
measure: Change in serum creatinine from baseline to Day 14
timeFrame: Day 14
Secondary outcomes:
measure: To compare four SLV320 doses to placebo on the change in the following variables: Dyspnea (Likert Scale and PDA scale), eGFR (MDRD Formula), Subject Global Clinical Assessment Score, Urine Osmolality, Serum Osmolality
timeFrame: Up to Day 3 (Dyspnea); Up to Day 4 (Urine Osmolality); Up to Day 60 (eGFR, Subject Global Clinical Assessment Score, Serum Osmolality)
measure: To compare the effect of four I.V. doses of SLV320 with placebo using the trichotomous endpoint of treatment success, treatment failure, or no change
timeFrame: Up to Day 14
measure: To compare the effect of four I.V. doses of SLV320 with placebo on top of diuretic use
timeFrame: Up to Day 3
measure: To compare the effect of four I.V. doses of SLV320 with placebo using a composite endpoint of all-cause mortality, cardiovascular hospitalization or hospitalization for worsening renal function, in time to event and frequency
timeFrame: Up to Day 180
measure: To determine the pharmacokinetic profile of I.V. SLV320
timeFrame: Up to Day 3
Other outcomes:
Locations:
city: Alameda
country: United States
facility: S320.2.011 Site # 548
state: California
city: Banning
country: United States
facility: S320.2.011 Site # 566
state: California
city: Inglewood
country: United States
facility: S320.2.011 Site # 551
state: California
city: Bridgeport
country: United States
facility: S320.2.011 Site # 564
state: Connecticut
city: Hollywood
country: United States
facility: S320.2.011 Site # 505
state: Florida
city: Jacksonville
country: United States
facility: S320.2.011 Site # 507
state: Florida
city: Riverdale
country: United States
facility: S320.2.011 Site # 532
state: Georgia
city: Chicago
country: United States
facility: S320.2.011 Site # 513
state: Illinois
city: Indianapolis
country: United States
facility: S320.2.011 Site # 561
state: Indiana
city: Owensboro
country: United States
facility: S320.2.011 Site # 526
state: Kentucky
city: Natchitoches
country: United States
facility: S320.2.011 Site # 504
state: Louisiana
city: Biddeford
country: United States
facility: S320.2.011 Site # 546
state: Maine
city: Dearborn
country: United States
facility: S320.2.011 Site # 523
state: Michigan
city: Detroit
country: United States
facility: S320.2.011 Site # 534
state: Michigan
city: Detroit
country: United States
facility: S320.2.011 Site # 558
state: Michigan
city: St. Louis
country: United States
facility: S320.2.011 Site # 508
state: Missouri
city: Brooklyn
country: United States
facility: S320.2.011 Site # 541
state: New York
city: New York
country: United States
facility: S320.2.011 Site # 537
state: New York
city: Akron
country: United States
facility: S320.2.011 Site # 521
state: Ohio
city: Toledo
country: United States
facility: S320.2.011 Site # 527
state: Ohio
city: Philadelphia
country: United States
facility: S320.2.011 Site # 528
state: Pennsylvania
city: Colombia
country: United States
facility: S320.2.011 Site # 510
state: South Carolina
city: Nashville
country: United States
facility: S320.2.011 Site # 545
state: Tennessee
city: Tullahoma
country: United States
facility: S320.2.011 Site # 519
state: Tennessee
city: Houston
country: United States
facility: S320.2.011 Site # 511
state: Texas
city: San Antonio
country: United States
facility: S320.2.011 Site # 518
state: Texas
city: Manitowoc
country: United States
facility: S320.2.011 Site # 556
state: Wisconsin
city: Milwaukee
country: United States
facility: S320.2.011 Site # 565
state: Wisconsin
city: Montreal
country: Canada
facility: S320.2.011 Site # 601
city: Santiago
country: Chile
facility: S320.2.011 Site # 427
city: Viña del Mar
country: Chile
facility: S320.2.011 Site # 433
city: Viña del Mar
country: Chile
facility: S320.2.011 Site # 434
city: Aarhus
country: Denmark
facility: S320.2.011 Site # 100
city: Aarhus
country: Denmark
facility: S320.2.011 Site # 102
city: Esbjerg
country: Denmark
facility: S320.2.011 Site # 103
city: Frederiksberg
country: Denmark
facility: S320.2.011 Site # 106
city: Herning
country: Denmark
facility: S320.2.011 Site # 105
city: København
country: Denmark
facility: S320.2.011 Site # 104
city: Dijon
country: France
facility: S320.2.011 Site # 125
city: Lille
country: France
facility: S320.2.011 Site # 123
city: Paris
country: France
facility: S320.2.011 Site # 121
city: Pessac
country: France
facility: S320.2.011 Site # 124
city: Pontoise
country: France
facility: S320.2.011 Site # 126
city: Toulouse
country: France
facility: S320.2.011 Site # 128
city: Bad Nauheim
country: Germany
facility: S320.2.011 Site # 182
city: Berlin
country: Germany
facility: S320.2.011 Site # 187
city: Frankfurt
country: Germany
facility: S320.2.011 Site # 186
city: Hannover
country: Germany
facility: S320.2.011 Site # 180
city: Limburg
country: Germany
facility: S320.2.011 Site # 185
city: Mannheim
country: Germany
facility: S320.2.011 Site # 190
city: Weiden
country: Germany
facility: S320.2.011 Site # 188
city: Aosta
country: Italy
facility: S320.2.011 Site # 146
city: Cremona
country: Italy
facility: S320.2.011 Site # 145
city: Genova
country: Italy
facility: S320.2.011 Site # 142
city: Milano
country: Italy
facility: S320.2.011 Site # 149
city: Modena
country: Italy
facility: S320.2.011 Site # 140
city: Orbassano
country: Italy
facility: S320.2.011 Site # 143
city: Bialystok
country: Poland
facility: S320.2.011 Site # 250
city: Inowroclaw
country: Poland
facility: S320.2.011 Site # 231
city: Krakow
country: Poland
facility: S320.2.011 Site # 236
city: Lodz
country: Poland
facility: S320.2.011 Site # 249
city: Olawa
country: Poland
facility: S320.2.011 Site # 243
city: Plock
country: Poland
facility: S320.2.011 Site # 251
city: Poznan
country: Poland
facility: S320.2.011 Site # 240
city: Przeworsk
country: Poland
facility: S320.2.011 Site # 247
city: Pulawy
country: Poland
facility: S320.2.011 Site # 242
city: Radom
country: Poland
facility: S320.2.011 Site # 239
city: Ruda Slaska
country: Poland
facility: S320.2.011 Site # 232
city: Starogard Gdanski
country: Poland
facility: S320.2.011 Site # 245
city: Torun
country: Poland
facility: S320.2.011 Site # 234
city: Torun
country: Poland
facility: S320.2.011 Site # 248
city: Tychy
country: Poland
facility: S320.2.011 Site # 238
city: Wroclaw
country: Poland
facility: S320.2.011 Site # 233
city: Baia Mare
country: Romania
facility: S320.2.011 Site # 265
city: Braila
country: Romania
facility: S320.2.011 Site # 262
city: Bucuresti
country: Romania
facility: S320.2.011 Site # 260
city: Bucuresti
country: Romania
facility: S320.2.011 Site # 263
city: Bucuresti
country: Romania
facility: S320.2.011 Site # 267
city: Suceava
country: Romania
facility: S320.2.011 Site # 264
city: Targoviste
country: Romania
facility: S320.2.011 Site # 261
city: Timisoara
country: Romania
facility: S320.2.011 Site # 266
city: Kazan
country: Russian Federation
facility: S320.2.011 Site # 294
city: Krasnodar
country: Russian Federation
facility: S320.2.011 Site # 306
city: Moscow
country: Russian Federation
facility: S320.2.011 Site # 290
city: Moscow
country: Russian Federation
facility: S320.2.011 Site # 297
city: Moscow
country: Russian Federation
facility: S320.2.011 Site # 299
city: Moscow
country: Russian Federation
facility: S320.2.011 Site # 301
city: Moscow
country: Russian Federation
facility: S320.2.011 Site # 303
city: Moscow
country: Russian Federation
facility: S320.2.011 Site # 304
city: Moscow
country: Russian Federation
facility: S320.2.011 Site # 305
city: Saint-Petersburg
country: Russian Federation
facility: S320.2.011 Site # 291
city: Saint-Petersburg
country: Russian Federation
facility: S320.2.011 Site # 292
city: Saint-Petersburg
country: Russian Federation
facility: S320.2.011 Site # 298
city: Saint-Petersburg
country: Russian Federation
facility: S320.2.011 Site # 302
city: St. Petersburg
country: Russian Federation
facility: S320.2.011 Site # 300
city: Voronezh
country: Russian Federation
facility: S320.2.011 Site # 293
city: Yaroslavl
country: Russian Federation
facility: S320.2.011 Site # 295
city: Dnipropetrovsk
country: Ukraine
facility: S320.2.011 Site # 335
city: Ivano-Frankivsk
country: Ukraine
facility: S320.2.011 Site # 332
city: Kharkiv
country: Ukraine
facility: S320.2.011 Site # 334
city: Kyiv
country: Ukraine
facility: S320.2.011 Site # 330
city: Kyiv
country: Ukraine
facility: S320.2.011 Site # 338
city: Lugansk
country: Ukraine
facility: S320.2.011 Site # 331
city: Lutsk
country: Ukraine
facility: S320.2.011 Site # 333
city: Odessa
country: Ukraine
facility: S320.2.011 Site # 337
Study officials:
affiliation: Solvay Pharmaceuticals
name: Robyn Bethany
role: STUDY_DIRECTOR
References:
citation: Pang PS, Mehra M, Maggioni AP, Filippatos G, Middlebrooks J, Turlapaty P, Kazei D, Gheorghiade M; RENO-DEFEND Investigators. Rationale, design, and results from RENO-DEFEND 1: a randomized, dose-finding study of the selective A1 adenosine antagonist SLV320 in patients hospitalized with acute heart failure. Am Heart J. 2011 Jun;161(6):1012-23.e3. doi: 10.1016/j.ahj.2011.03.004.