In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
This is a prospective observational study, using the Vermont Oxford Network (VON) Registry, Burlington, Vermont:
this is a non-profit voluntary collaboration of health care professionals dedicated to improving the quality and safety of medical care for newborn infants and their families, established in 1988. The sponsor will provide each hospital that purchases a Cool-Cap with information on the existing VON. This network maintains a dataset including information about the care and outcomes of high-risk newborn infants. The sponsor explains to the hospitals that purchases the device how to join the VON, who to contact, and an explanation of how their participation can help in monitoring the use of this new treatment. The VON is independently establishing a registry for infants with symptoms of hypoxic ischemic encephalopathy (HIE). Patients receiving the Cool-Cap for HIE will be included in this registry. VON will collect data for this registry through a software module added to the system currently used by their members to report data for their other registries.
Study Population Description
Study population is as per device indication. The device is indicated for use in fullterm
infants with clinical evidence of moderate to severe hypoxic-ischemic encephalopathy (HIE)*. Cool-Cap provides selective head cooling with mild systemic hypothermia to prevent or reduce the severity of neurologic injury associated with HIE.
No sample size or power calculations are provided in the protocol.The sponsor expects that participation
in the registry will be a subset of all Cool-Cap customers/patients. It is expected that a reasonable percentage of hospitals will already be a member of this registry and will participate.
Data to be collected on infants treated with the Cool-Cap will include the following information.
Demographic and Admission data: sec, race / ethnicity, measurements at birth (weight, head circumference, length), gestational age, gestational category (AGA, LGA, SGA <10%), date of birth, time of birth, inborn or transfer, method of delivery, multiple births, delivery complications, NICU admit temperature, Apgar scores, CFM / aEEG Score, Sarnat Stage, cord pH, base deficit, assisted ventilation, cooling start date/time, cooling stop date/time, stop date/time, restart date/time, duration, and reason for any interruptions of cooling that exceed 30 minutes. Data that reports the occurrence of potential serious adverse events due to hypothermia as defined in the clinical trial protocol. This would include: - Major cardiac arrhythmia (such as ventricular tachycardia, ventricular fibrillation or acquired conduction block), - Major venous thrombosis not related to an infusion line,- Severe hypotension despite full inotrope support and volume correction,Data that reports the occurrence of adverse events encountered in the clinical trial. This would include:- Clinical seizures during rewarming,- Abnormal EKG (minor cardiac arrhythmia or prolonged QT interval),- Scalp edema,- Sclerema neonatorum,Data that will provide information on the infant's condition when discharged from the hospital would include:- Discharge Date,- Discharge Diagnosis or Cause of Death
Followup Visits and Length of Followup
The sponsor will discontinue participation in the registry, and reporting of data, after 5 years.
Final Study Results
Actual Number of Patients Enrolled
Actual Number of Sites Enrolled
Patient Followup Rate
Final Safety Findings
Infants in the current registry had higher rates of adverse events including minor cardiac arrhythmias,
seizures, and scalp edema than those in the randomized clinical trial; this trend does not appear to change over time. The sponsor has provided explanations on the observed difference, which was mainly due to the longer observational period and different definitions of adverse events in PAS contrast to the PMA data
Final Effectiveness Findings
Effectiveness findings were not reported.
Study Strengths and Weaknesses
Although important data was collected about patient characteristics and adverse events for these infants during
their NICU hospitalization, the registry may not be able to provide any useful information in assessing device performance (safety and effectiveness) under actual conditions
of use because of its following limitations: (1) lack of valid comparison group; (2) potential selection bias due to the lack of baseline information on infants who may receive the device but whose data were not entered in the registry; (3) no continued follow-up for premarket and continued access patients who have already received the device; (4) failure to obtain data on infants after discharge from the NICU; and (5) no long-term follow-up with neurodevelopmental assessments.
Recommendations for Labeling Changes
The sponsor was asked to update their labeling to reflect the changes in clinical practice
of therapeutic hypothermia for neonatal HIE based on the final PAS