Cardiomyopathies, Heart Failure
Conditions
Keywords
Ventricular Assist Device, Pediatric Ventricular Assist Device
Brief summary
The purpose of the study is to determine whether use of the Berlin Heart EXCOR® Pediatric Ventricular Assist Device for bridge-to-transplant is associated with a reasonable assurance of safety and probable benefit such that the EXCOR® Pediatric merits approval by the Food and Drug Administration under a Humanitarian Device Exception (HDE).
Detailed description
Berlin Heart Inc. is sponsoring a prospective, multi-center, single arm study to access the safety and probable benefit of the Berlin Heart EXCOR® Pediatric Ventricular Assist Device \[EXCOR® Pediatric\]. The study will compare the EXCOR® Pediatric with a historical control population supported with extra-corporeal membrane oxygenation (ECMO) as a bridge to cardiac transplantation in children.
Interventions
DEVICEEXCOR Pediatric
Extracorporeal Ventricular Assist Device
Sponsors
Berlin Heart, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 16 Years
Healthy volunteers
No
Inclusion criteria
\- Severe New York Heart Association (NYHA) Functional Class IV (or Ross Functional Class IV for patients \<= 6 years) heart failure refractory to optimal medical therapy, and has met at least one of the following criteria: * Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile status 1 or 1a, i.e. critical cardiogenic shock (low BP unresponsive to support), compromised end organ perfusion, \< 24 hour survival without mechanical support; may be due to Ventricular Tachycardia (VT)/Ventricular Fibrillation (VF) (1A) OR * INTERMACS profile status or 2A (i.e progressive decline): not in imminent danger, but worsening despite optimal inotropic therapy; may be due to VT/VF (2A) AND at least one of the following criteria: Decline in renal functions, Decline in nutritional status, Decline in mobility/ambulation OR * Support with extra-corporeal membrane oxygenation (ECMO) or other mechanical circulatory support device OR * Unable to separate from cardiopulmonary bypass * Listed (UNOS status 1A or equivalent) for cardiac transplantation * Two-ventricle circulation, including cardiomypathy, repaired structural heart disease or acquired heart disease * Age 0 to 16 years * Weight \>= 3 kg and \<= 60 kg * Legal guardian (and patient if age-appropriate) understands the nature of the procedure, is willing to comply with associated follow-up evaluations, and provide written informed consent and assent prior to the procedure
Exclusion criteria
* Support on ECMO for \>= 10 days * Cardiopulmonary resuscitation (CPR) duration \>= 30 minutes within 48 hours of implantation * Body weight \< 3.0 kg or Body Surface Area \> 1.5 m2 * Presence of mechanical aortic valve * Unfavorable or technically-challenging cardiac anatomy including single ventricle lesions, complex heterotaxy, and restrictive cardiomyopathy * Evidence of intrinsic hepatic disease * Evidence of intrinsic renal disease * Evidence of intrinsic pulmonary disease * Hemodialysis or peritoneal dialysis (not including dialysis or continuous veno-venous hemofiltration (CVVH) for fluid removal) * Moderate or severe aortic and/or pulmonic valve insufficiency * Apical Ventricular Septal Defects (VSD) or other compromise that is technically challenging to repair at implant * Documented heparin induced thrombocytopenia (HIT) * Documented coagulopathy * Hematologic disorder * Active Infection within 48 hours of implant (positive blood culture or White Blood Cell Count \>15,000 and fever \> 38 degrees C) * Documented Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) * Evidence of recent life-limiting malignant disease * Stroke within 30 days prior to enrollment * Psychiatric or behavioral disease * Currently participating in another Investigational Device Exemption (IDE) or Investigational New Drug Application (IND) trial * Patient is pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Safety of EXCOR® Pediatric Was Evaluated by Summarizing the Serious Adverse Event Rate Experienced While the Subject Was Supported on the Device. | Participants were followed while on device support, an average of 58 days | The serious adverse event rate was calculated by totaling the number of serious adverse events all subjects experienced during device support (from implant to explant, an average of 58 days) divided by the total support time (in days) for all subjects. The serious adverse event rates were calculated separately for each primary study cohort. |
| Efficacy of the EXCOR® Pediatric Was Estimated by Showing Survival of All Participants Who Were Supported by the Device. | Participants were followed while on device support, an average of 58 days | Efficacy of the EXCOR® Pediatric was estimated by showing survival of all participants who were supported by the device. |
Countries
Canada, United States
Participant flow
Recruitment details
Subject were recruited at pediatric transplant centers by the implanting physicians.
Participants by arm
| Arm | Count |
|---|---|
| EXCOR Pediatric Implantation of the EXCOR Pediatric Ventricular Assist Device | 48 |
| Total | 48 |
Baseline characteristics
| Characteristic | EXCOR Pediatric |
|---|---|
| Age, Categorical <=18 years | 48 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 64.3 Months |
| Region of Enrollment Canada | 1 participants |
| Region of Enrollment United States | 47 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 48 |
| serious Total, serious adverse events | 41 / 48 |
Outcome results
Primary
Efficacy of the EXCOR® Pediatric Was Estimated by Showing Survival of All Participants Who Were Supported by the Device.
Efficacy of the EXCOR® Pediatric was estimated by showing survival of all participants who were supported by the device.
Time frame: Participants were followed while on device support, an average of 58 days
Population: All subjects implanted with the device were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Efficacy of the EXCOR® Pediatric Was Estimated by Showing Survival of All Participants Who Were Supported by the Device. | 21 participants |
| Cohort 2 | Efficacy of the EXCOR® Pediatric Was Estimated by Showing Survival of All Participants Who Were Supported by the Device. | 22 participants |
Primary
The Safety of EXCOR® Pediatric Was Evaluated by Summarizing the Serious Adverse Event Rate Experienced While the Subject Was Supported on the Device.
The serious adverse event rate was calculated by totaling the number of serious adverse events all subjects experienced during device support (from implant to explant, an average of 58 days) divided by the total support time (in days) for all subjects. The serious adverse event rates were calculated separately for each primary study cohort.
Time frame: Participants were followed while on device support, an average of 58 days
Population: All 48 participants were included in the analysis. Adverse Events for each participant was counted and the total number of events was divided by the total time the Cohort's subjects were supported on device. A 95% Poisson confidence interval was calculated around the point estimates.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | The Safety of EXCOR® Pediatric Was Evaluated by Summarizing the Serious Adverse Event Rate Experienced While the Subject Was Supported on the Device. | 0.068 Events per patient-day |
| Cohort 2 | The Safety of EXCOR® Pediatric Was Evaluated by Summarizing the Serious Adverse Event Rate Experienced While the Subject Was Supported on the Device. | 0.066 Events per patient-day |
Comparison: Ho: EXCOR® SAE Rate \>=0.25 Ha: EXCOR® SAE Rate \< 0.25 Where serious adverse event (SAE) rate is calculated as the total number of serious adverse events divided by the sum of days all patients are on the EXCOR® Pediatric device, and 0.25 serious adverse events per patient-day is the success criterion. Study success in terms of safety will be demonstrated by the upper bound of a two-sided 95% Poisson exact confidence interval being less than 0.25.p-value: <0.0595% CI: [0, 0.25]Poisson confidence interval