Clinical trial NCT02151383: Pharmacokinetics & Safety of Serelaxin on Top of Standard of Care Therapy in Pediatric Patients With Acute Heart Failure
Official title: Multicenter, Open-label, Dose Escalation Study to Evaluate Safety, Tolerability and Pharmacokinetics of RLX030 in Addition to Standard of Care in Pediatric Patients From Birth to <18 Years of Age, Hospitalized With Acute Heart Failure
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Heart Failure
Keywords: Acute heart failure
RELAX-AHF-PEDIATRIC PK
AHF
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-05-30
Enrollment: 12
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study was to evaluate the safety, tolerability and pharmacokinetics of an intravenous infusion of serelaxin on top of standard of care therapy, in pediatric patients with acute heart failure (AHF)

Detailed description: The study was terminated early and the pediatric development of serelaxin in the treatment of acute heart failure (AHF) discontinued, following the results of the phase III study RELAX-AHF-2 (CRLX030A2301/NCT01870778) study in adult patients with AHF. Whilst no new safety concerns associated with serelaxin were observed, the study in adults did not meet either of its primary endpoints

Eligibility criteria: Key Inclusion criteria:

* Body weight ≥2.5 kg to ≤120 kg
* Hospitalized in an intensive care unit or step-down unit with the following:
* - Signs and symptoms of acute heart failure of any etiology
* - Stable dose of vasoactive and/or inotropic drugs
* - For non-surgical patients echocardiographic evidence of reduced ventricular function (ejection fraction \<50% or fractional shortening \<28%)
* Systolic blood pressure (SBP) ≥25th percentile SBP for age and gender.

Key Exclusion criteria:

* Moderate to severe left ventricular outflow tract, mitral stenosis, or aortic arch obstruction
* Single ventricle physiology
* Fixed pulmonary hypertension
* Blood lactate levels \>5 mmol/L at screening
* Birth \< 36 weeks post-conceptual age (for patients \<1year old)
* Confirmed or clinically suspected systemic infection or severe localized infection
* Dyspnea or acute lung injury primarily due to non-cardiac causes
* Patients with severe renal impairment, those known to have significant renal disease and those having renal replacement therapy
* High use of inotropic and/or vasoactive agents at screening
* Electrocardiographic abnormalities
* Solid organ transplant recipient within 1 year of transplantation or one who presents with severe organ rejection

Primary outcomes:
measure: Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death
timeFrame: through 28 days + 30 days SAE follow up after completion or discontinuation from the study
measure: Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
timeFrame: at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28
measure: Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day)
timeFrame: at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28
Secondary outcomes:
measure: Change From Baseline in Mean Left Arterial Pressure for Low Dose (3-10-30 ug/kg/Day)
timeFrame: baseline, prior to each dose escalation, and at 24 hr. post end of infusion
measure: Change From Baseline in Mean Left Arterial Pressure for High Dose (10 -30-100 ug/kg/Day)
timeFrame: baseline, prior to each dose escalation, and at 24 hr. post end of infusion
measure: Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day3: 24 hours post infusion
measure: Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for High Dose (10-30-100 ug/kg/Day)
timeFrame: Day 1: hour 0 and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for High Dose (10-30-100 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
measure: Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for High Dose (10-30-100 ug/kg/Day)
timeFrame: Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Other outcomes:
Locations:
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Bronx
country: United States
facility: Novartis Investigative Site
state: New York
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Charleston
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Genève
country: Switzerland
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: