Severe Respiratory Syncytial Virus Infection
Conditions
Keywords
Infection, Arrhythmia, Death, Palivizumab, Safety, Hemodynamically Significant Congenital Heart Disease, Pediatric, Observational
Brief summary
Retrospective medical record review study of specific adverse events in children with congenital heart disease who received palivizumab for prophylaxis of serious respiratory syncytial virus infection and control subjects that did not receive palivizumab
Detailed description
This is an observational, non-interventional, retrospective cohort study of infants with hemodynamically significant congenital heart disease (HSCHD) who were less than 24 months of age when the first dose of palivizumab was administered (CASES), and infants who were diagnosed with hemodynamically significant congenital heart disease but did not receive palivizumab in a historical respiratory syncytial virus (RSV) season during the first 24 months of life (CONTROLS). CASES are matched to CONTROLS based on RSV season, age, type of cardiac lesion, and type of prior corrective cardiac surgery. Subject medical records are reviewed for occurrences of the clinical end points of infection, arrhythmia, and/or death that meet criteria for serious adverse events. The groups will be compared for number and percent of subjects who experience these primary serious adverse events (both individually and collectively) during a defined 8-month chart review period.
Interventions
None listed
Sponsors
Abbott
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Months
Healthy volunteers
No
Inclusion criteria
1. Subject must have documented hemodynamically significant congenital heart disease (Note: Children with uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus are not eligible). 2. Subject must have unoperated or partially corrected congenital heart disease. 3. Subject must have received at least one dose of palivizumab for prophylaxis during the Respiratory Syncytial Virus season - September 1 through April 30 (CASES), or would have been considered eligible for palivizumab prophylaxis (CONTROLS). 4. Subject must be \< 24 months of age at the time of the first dose of palivizumab prophylaxis (CASES) or \< 32 months of age at the end of the assigned Respiratory Syncytial Virus season in which they would have been eligible to receive palivizumab if the drug had been approved in the European Union (CONTROLS). 5. Subject's parent, guardian, or legal representative has voluntarily signed and dated a Release of Information Form to allow the review of medical records and collection of pertinent study data.
Exclusion criteria
1. Subject was contraindicated for treatment with palivizumab according to the current European product label. 2. Subject had full correction of Congenital Heart Disease. 3. Subject received palivizumab before approval for use in Congenital Heart Disease (CASES), or subject received palivizumab at any time (CONTROLS). 4. Subject has already been included in this study in a prior Respiratory Syncytial Virus season.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Infection, Serious Arrhythmia and/or Death | 8-month chart review period in CASES and CONTROLS | The number of subjects who experienced at least 1 event of infection, arrhythmia, or death meeting any of the criteria for a serious adverse event |
| Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Infection. | 8-month chart review period in CASES and CONTROLS | The number of subjects who experienced at least 1 event of infection meeting any of the criteria for a serious adverse event |
| Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Arrhythmia | 8-month chart review period in CASES and CONTROLS | The number of subjects who experienced at least 1 event of arrhythmia meeting any of the criteria for a serious adverse event |
| Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Death | 8-month chart review period in CASES and CONTROLS | The number of subjects who died |
Countries
Austria, Belgium, France, Germany, Italy, Norway, Poland, Slovenia, Spain, United Kingdom
Participant flow
Recruitment details
Infants diagnosed with hemodynamically significant congenital heart disease who were less than 24 months of age when first dosed with palivizumab (CASES) were compared for the occurrence of serious adverse events over an 8-month chart review period with matched infants who did not receive palivizumab during the first 24 months of life (CONTROLS).
Participants by arm
| Arm | Count |
|---|---|
| Palivizumab-treated Subjects (CASES) HSCHD infants, \<2 yrs old at first dose of palivizumab | 1,009 |
| Non-palivizumab-treated Subjects (CONTROLS) HSCHD infants, \<2 yrs old that did not receive palivizumab | 1,009 |
| Total | 2,018 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Subject Chart Review | died before chart review period | 0 | 2 |
| Subject Chart Review | matched partner excluded (reasons above) | 6 | 3 |
| Subject Chart Review | no data collected due to site closure | 3 | 4 |
| Subject Matching | eligible but not matched | 130 | 403 |
Baseline characteristics
| Characteristic | Palivizumab-treated Subjects (CASES) | Non-palivizumab-treated Subjects (CONTROLS) | Total |
|---|---|---|---|
| Age Categorical <=6 months | 651 participants | 656 participants | 1307 participants |
| Age Categorical >6 months | 358 participants | 353 participants | 711 participants |
| Age Continuous | 5.4 months STANDARD_DEVIATION 4.91 | 5.4 months STANDARD_DEVIATION 5.05 | 5.4 months STANDARD_DEVIATION 4.98 |
| Cardiac lesion Acyanotic | 521 participants | 522 participants | 1043 participants |
| Cardiac lesion Cyanotic | 488 participants | 487 participants | 975 participants |
| Corrective cardiac surgery Fully corrected congenital heart disease | 0 participants | 3 participants | 3 participants |
| Corrective cardiac surgery None | 484 participants | 485 participants | 969 participants |
| Corrective cardiac surgery Partially corrected congenital heart disease | 525 participants | 521 participants | 1046 participants |
| Region of Enrollment Austria | 96 participants | 53 participants | 149 participants |
| Region of Enrollment Belgium | 77 participants | 115 participants | 192 participants |
| Region of Enrollment France | 188 participants | 211 participants | 399 participants |
| Region of Enrollment Germany | 97 participants | 90 participants | 187 participants |
| Region of Enrollment Italy | 111 participants | 42 participants | 153 participants |
| Region of Enrollment Norway | 12 participants | 7 participants | 19 participants |
| Region of Enrollment Poland | 36 participants | 242 participants | 278 participants |
| Region of Enrollment Slovenia | 16 participants | 20 participants | 36 participants |
| Region of Enrollment Spain | 284 participants | 170 participants | 454 participants |
| Region of Enrollment United Kingdom | 92 participants | 59 participants | 151 participants |
| Sex: Female, Male Female | 437 Participants | 462 Participants | 899 Participants |
| Sex: Female, Male Male | 572 Participants | 547 Participants | 1119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 303 / 1,009 | 349 / 1,009 |
Outcome results
Primary
Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Death
The number of subjects who died
Time frame: 8-month chart review period in CASES and CONTROLS
Population: The population analyzed included the full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palivizumab-treated Subjects (CASES) | Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Death | 9 participants |
| Non-palivizumab-treated Subjects (CONTROLS) | Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Death | 10 participants |
Comparison: The null hypothesis was that the odds ratio was greater than or equal to 2. The planned sample size of 2000 participants (1000 participants in each group) provided greater than 90% power to determine non-inferiority based on the odds ratio less than 2.exact binomial
Primary
Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Arrhythmia
The number of subjects who experienced at least 1 event of arrhythmia meeting any of the criteria for a serious adverse event
Time frame: 8-month chart review period in CASES and CONTROLS
Population: The population analyzed included the full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palivizumab-treated Subjects (CASES) | Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Arrhythmia | 41 participants |
| Non-palivizumab-treated Subjects (CONTROLS) | Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Arrhythmia | 39 participants |
Comparison: The null hypothesis was that the odds ratio was greater than or equal to 2. The planned sample size of 2000 participants (1000 participants in each group) provided greater than 90% power to determine non-inferiority based on the odds ratio less than 2.exact binomial
Primary
Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Infection.
The number of subjects who experienced at least 1 event of infection meeting any of the criteria for a serious adverse event
Time frame: 8-month chart review period in CASES and CONTROLS
Population: The population analyzed included the full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palivizumab-treated Subjects (CASES) | Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Infection. | 281 participants |
| Non-palivizumab-treated Subjects (CONTROLS) | Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Infection. | 329 participants |
Comparison: The null hypothesis was that the odds ratio was greater than or equal to 2. The planned sample size of 2000 participants (1000 participants in each group) provided greater than 90% power to determine non-inferiority based on the odds ratio less than 2.exact binomial
Primary
Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Infection, Serious Arrhythmia and/or Death
The number of subjects who experienced at least 1 event of infection, arrhythmia, or death meeting any of the criteria for a serious adverse event
Time frame: 8-month chart review period in CASES and CONTROLS
Population: The population analyzed included the full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palivizumab-treated Subjects (CASES) | Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Infection, Serious Arrhythmia and/or Death | 303 participants |
| Non-palivizumab-treated Subjects (CONTROLS) | Comparison Between CASES and CONTROLS of the Occurrence of Specific Clinical Outcomes of Serious Infection, Serious Arrhythmia and/or Death | 349 participants |
Comparison: The null hypothesis was that the odds ratio was greater than or equal to 2. The planned sample size of 2000 participants (1000 participants in each group) provided greater than 90% power to determine non-inferiority based on the odds ratio less than 2.exact binomial