Respiratory Syncytial Virus Infection
Conditions
Keywords
Prevention of severe RSV infection, Respiratory syncytial virus (RSV) infection, Down Syndrome, Immunocompromised, Effectiveness of palivizumab
Brief summary
This post marketing observational study (PMOS) was conducted in Japan during the 2013-2014 and 2014-2015 Respiratory Syncytial Virus (RSV) seasons to assess the safety and effectiveness of palivizumab for the prevention of serious lower respiratory tract infection caused by RSV in participants 24 months of age and under, who have an immunocompromised medical condition (e.g., combined immunodeficiency disease, antibody deficiency, or other types of immunodeficiency; HIV infection; recovering from organ or bone marrow transplantation; on chemotherapy; on high-dose corticosteroid therapy; on immunosuppressants) or who have Down syndrome.
Detailed description
Palivizumab was prescribed according to the local label and independently of the decision to enroll participants in the study. Palivizumab was administered monthly throughout the Respiratory Syncytial Virus (RSV) infection seasons via intramuscular injection at a dose of 15 mg/kg of body weight. Survey forms were collected after the observation period. The number of adverse events and the frequency of hospitalizations due to RSV infections in surveyed participants were assessed to evaluate the safety and effectiveness of palivizumab.
Interventions
None listed
Sponsors
AbbVie
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Months
Healthy volunteers
No
Inclusion criteria
1. Availability of a parent or legal guardian who was capable and willing to give written informed consent for his/her newborn, infant or young child to participate in the study 2. Participants receiving palivizumab for prevention of serious lower respiratory tract disease caused by RSV infection 3. Newborns, infants, or young children 24 months of age and under who have an immunocompromised medical condition: * combined immunodeficiency, (severe combined immunodeficiency, X-linked hyper-immunoglobulin M (IgM) syndrome, etc.), antibody deficiency (X-linked agammaglobulinemia,common variable immunodeficiency, non-X-linked hyper-IgM syndrome,etc.) or other immunodeficiency (Wiskott-Aldrich syndrome, etc.) * acquired T cell dysfunction ( such as human immunodeficiency virus (HIV) infection etc.) * history of past organ transplantation * history of past bone marrow transplantation * receiving immunosuppressive chemotherapy * receiving systemic high-dose corticosteroid therapy (prednisone equivalents ≥ 0.5 mg/kg/every other day, other than inhaler or topical use), or * receiving other immunosuppressive therapy (azathioprine, methotrexate, mizoribine, mycophenolate mofetil, cyclophosphamide, cyclosporine, tacrolimus, cytokine inhibitors, etc.) * receiving biologics (including cytokine inhibitors) * Others (nephrotic syndrome, chronic peritoneal dialysis, hemodialysis) 4. Newborns, infants, or young children age of 24 months and under who have Down syndrome without a current hemodynamically significant Congenital Heart Disease. The participant must have had an experience with persistent respiratory symptoms or regular outpatient treatment due to respiratory tract infection prior to current RSV season.
Exclusion criteria
1. Participants included in the Contraindications section of the package insert 2. Participants with known hypersensitivity to the ingredients of palivizumab 3. Participants with a known positive RSV infection before hospitalization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks | An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with their treatment. Adverse events were documented on the case report form (CRF). |
| Number of Participants With Serious Adverse Events | From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks | A serious adverse event was defined as any untoward medical occurrence in a participant that the investigator believed to be causally related to the study treatment and met at least one of the following criteria: death, life-threatening, hospitalization or prolongation of hospitalization, persistent or significant disability/incapacity, or important medical event requiring medical or surgical intervention to prevent serious outcome. Serious adverse events were documented on the case report form (CRF). |
| Number of Participants With Adverse Drug Reactions | From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks | An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with their treatment. If a causal relationship with palivizumab was: Related, Causality cannot be ruled out, or Not assessable as determined by the investigator, it was classified as an adverse drug reaction (ADR). An AE was considered a serious adverse event (SAE) and a serious adverse drug reaction (SADR) if the severity of the AE or ADR was any one of the following, as determined by the investigator: Death, Life-threatening condition, Hospitalization or prolonged hospitalization, Persistent or significant disability, or Other medically important condition. Information about AEs and ADRs was documented on the case report form (CRF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Hospitalized Participants Requiring Respiratory Support | From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks | The presence/absence of respiratory support, (oxygen therapy, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure, and other mechanical respiratory support or Intensive Care Unit admission) the start and end dates of respiratory support, and the dates of hospitalization and discharge were documented on the case report form (CRF). |
| Change in Lower Respiratory Tract Infection (LRI) Score During the Study | From the first administration of palivizumab up to the last administration of palivizumab, up to 36 weeks | The Lower Respiratory Tract Infection (LRI) Score ranged from 0 (well or baseline); 1 (Upper Respiratory tract Infection \[URI\]), mild); 2 (LRI); 3 (LRI, moderate); 4 (LRI, severe) to 5 (Respiratory Failure). Components of the score included respiratory rate per minute, oxygen saturation, and physical findings of LRI. LRI scores were documented on the case report form (CRF). |
| Mean Duration of Respiratory Support | From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks | The presence/absence of respiratory support (oxygen therapy, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure, and other mechanical respiratory support or Intensive Care Unit admission) and the start and end dates of respiratory support were documented on the case report form (CRF). |
| Number of Participants Hospitalized Due to Respiratory Syncytial Virus (RSV) Infection | From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks | Hospitalization due to RSV infection or the presence/absence of positive RSV antigen test results during hospitalization was documented on the case report form (CRF). |
| Mean Hospitalization Length Due to Respiratory Syncytial Virus (RSV) Infection | From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks | The date of hospitalization due to RSV infection and the date of hospital discharge were documented on the case report form (CRF). |
Participant flow
Pre-assignment details
Participants enrolled via consecutive enrollment method who had a completed CRF. Participants were excluded if there was enrollment at a non-contracting institution or beyond the contracted number; duplicate enrollment; no palivizumab administration; or if palivizumab administration began outside of the investigation period.
Participants by arm
| Arm | Count |
|---|---|
| Immunocompromised Children Children with immunocompromised conditions or Down syndrome at high-risk of serious RSV disease who received palivizumab during the RSV season | 304 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not meet inclusion criteria | 13 |
| Overall Study | Excluded from SAS: Duplication | 2 |
| Overall Study | Excluded from SAS: Early treatment | 2 |
| Overall Study | Excluded from SAS: Enrollment violation | 2 |
| Overall Study | Excluded from SAS: Ineligible for study | 2 |
| Overall Study | Hospitalized for RSV at study start | 3 |
Baseline characteristics
| Characteristic | Immunocompromised Children |
|---|---|
| Age at the start of treatment > 12 and ≤ 24 months | 137 Participants |
| Age at the start of treatment > 1 and ≤ 3 months | 24 Participants |
| Age at the start of treatment ≤ 1 month | 31 Participants |
| Age at the start of treatment > 24 months | 0 Participants |
| Age at the start of treatment > 3 and ≤ 6 months | 31 Participants |
| Age at the start of treatment > 6 and ≤ 12 months | 81 Participants |
| Age, Continuous | 11.9 months STANDARD_DEVIATION 7.5 |
| Body weight at birth ≥ 1000 and ≤ 1500 grams | 4 Participants |
| Body weight at birth < 1000 grams | 0 Participants |
| Body weight at birth ≥ 1500 and ≤ 2500 grams | 80 Participants |
| Body weight at birth ≥ 2500 and ≤ 4000 grams | 207 Participants |
| Body weight at birth ≥ 4000 grams | 2 Participants |
| Body weight at birth Not specified | 11 Participants |
| Body weight at the start of treatment ≥ 10000 and < 15000 grams | 45 Participants |
| Body weight at the start of treatment ≥ 1000 and < 1500 grams | 0 Participants |
| Body weight at the start of treatment < 1000 grams | 0 Participants |
| Body weight at the start of treatment ≥ 15000 grams | 1 Participants |
| Body weight at the start of treatment ≥ 1500 and < 2500 grams | 1 Participants |
| Body weight at the start of treatment ≥ 2500 and < 5000 grams | 52 Participants |
| Body weight at the start of treatment ≥ 5000 and < 10000 grams | 202 Participants |
| Body weight at the start of treatment Not specified | 3 Participants |
| Comorbidity No | 120 Participants |
| Comorbidity Unknown | 1 Participants |
| Comorbidity Yes- cardiovascular disease | 45 Participants |
| Comorbidity Yes- hepatic disease | 21 Participants |
| Comorbidity Yes- others | 142 Participants |
| Comorbidity Yes- renal disease | 18 Participants |
| Comorbidity Yes- respiratory disease | 50 Participants |
| Familial predisposition to hypersensitivity No | 180 Participants |
| Familial predisposition to hypersensitivity Not specified | 6 Participants |
| Familial predisposition to hypersensitivity Unknown | 84 Participants |
| Familial predisposition to hypersensitivity Yes | 34 Participants |
| Gestational age ≥ 22 and < 37 weeks | 56 Participants |
| Gestational age < 22 weeks | 0 Participants |
| Gestational age ≥ 37 and < 42 weeks | 237 Participants |
| Gestational age ≥ 42 weeks | 1 Participants |
| Gestational age Not specified | 10 Participants |
| Lower Respiratory Tract Infection score at the start of treatment 0 | 289 Participants |
| Lower Respiratory Tract Infection score at the start of treatment 1 | 5 Participants |
| Lower Respiratory Tract Infection score at the start of treatment 2 | 4 Participants |
| Lower Respiratory Tract Infection score at the start of treatment 3 | 4 Participants |
| Lower Respiratory Tract Infection score at the start of treatment 4 | 1 Participants |
| Lower Respiratory Tract Infection score at the start of treatment 5 | 1 Participants |
| Number of smokers in the household 0 smokers | 184 Participants |
| Number of smokers in the household ≥ 1 smokers | 40 Participants |
| Number of smokers in the household Not specified | 80 Participants |
| Participant's predisposition to hypersensitivity No | 245 Participants |
| Participant's predisposition to hypersensitivity Unknown | 28 Participants |
| Participant's predisposition to hypersensitivity Yes- allergic bronchitis | 1 Participants |
| Participant's predisposition to hypersensitivity Yes- allergic dermatitis | 4 Participants |
| Participant's predisposition to hypersensitivity Yes- allergic rhinitis | 4 Participants |
| Participant's predisposition to hypersensitivity Yes- asthma | 11 Participants |
| Participant's predisposition to hypersensitivity Yes- drug allergy | 3 Participants |
| Participant's predisposition to hypersensitivity Yes- food allergy | 11 Participants |
| Participant's predisposition to hypersensitivity Yes- others | 1 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black | 0 Participants |
| Race/Ethnicity, Customized Japanese | 297 Participants |
| Race/Ethnicity, Customized Others | 4 Participants |
| Race/Ethnicity, Customized White | 0 Participants |
| Sex: Female, Male Female | 117 Participants |
| Sex: Female, Male Male | 187 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 67 / 304 |
| serious Total, serious adverse events | 53 / 304 |
Outcome results
Primary
Number of Participants With Adverse Drug Reactions
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with their treatment. If a causal relationship with palivizumab was: Related, Causality cannot be ruled out, or Not assessable as determined by the investigator, it was classified as an adverse drug reaction (ADR). An AE was considered a serious adverse event (SAE) and a serious adverse drug reaction (SADR) if the severity of the AE or ADR was any one of the following, as determined by the investigator: Death, Life-threatening condition, Hospitalization or prolonged hospitalization, Persistent or significant disability, or Other medically important condition. Information about AEs and ADRs was documented on the case report form (CRF).
Time frame: From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Population: Participants enrolled via consecutive enrollment method who had a completed CRF. Participants were excluded if there was enrollment at a non-contracting institution or beyond the contracted number; duplicate enrollment; no palivizumab administration; or if palivizumab administration began outside of the investigation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunocompromised Children | Number of Participants With Adverse Drug Reactions | 25 Participants |
Primary
Number of Participants With Adverse Events
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with their treatment. Adverse events were documented on the case report form (CRF).
Time frame: From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Population: Participants enrolled via consecutive enrollment method who had a completed CRF. Participants were excluded if there was enrollment at a non-contracting institution or beyond the contracted number; duplicate enrollment; no palivizumab administration; or if palivizumab administration began outside of the investigation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunocompromised Children | Number of Participants With Adverse Events | 99 Participants |
Primary
Number of Participants With Serious Adverse Events
A serious adverse event was defined as any untoward medical occurrence in a participant that the investigator believed to be causally related to the study treatment and met at least one of the following criteria: death, life-threatening, hospitalization or prolongation of hospitalization, persistent or significant disability/incapacity, or important medical event requiring medical or surgical intervention to prevent serious outcome. Serious adverse events were documented on the case report form (CRF).
Time frame: From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Population: Participants enrolled via consecutive enrollment method who had a completed CRF. Participants were excluded if there was enrollment at a non-contracting institution or beyond the contracted number; duplicate enrollment; no palivizumab administration; or if palivizumab administration began outside of the investigation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunocompromised Children | Number of Participants With Serious Adverse Events | 53 Participants |
Secondary
Change in Lower Respiratory Tract Infection (LRI) Score During the Study
The Lower Respiratory Tract Infection (LRI) Score ranged from 0 (well or baseline); 1 (Upper Respiratory tract Infection \[URI\]), mild); 2 (LRI); 3 (LRI, moderate); 4 (LRI, severe) to 5 (Respiratory Failure). Components of the score included respiratory rate per minute, oxygen saturation, and physical findings of LRI. LRI scores were documented on the case report form (CRF).
Time frame: From the first administration of palivizumab up to the last administration of palivizumab, up to 36 weeks
Population: Participants with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immunocompromised Children | Change in Lower Respiratory Tract Infection (LRI) Score During the Study | 1 dose | 0.1 units on a scale | Standard Deviation 0.6 |
| Immunocompromised Children | Change in Lower Respiratory Tract Infection (LRI) Score During the Study | 2 doses | 0.1 units on a scale | Standard Deviation 0.6 |
| Immunocompromised Children | Change in Lower Respiratory Tract Infection (LRI) Score During the Study | 3 doses | 0.1 units on a scale | Standard Deviation 0.6 |
| Immunocompromised Children | Change in Lower Respiratory Tract Infection (LRI) Score During the Study | 4 doses | 0.1 units on a scale | Standard Deviation 0.6 |
| Immunocompromised Children | Change in Lower Respiratory Tract Infection (LRI) Score During the Study | 5 doses | 0.1 units on a scale | Standard Deviation 0.4 |
| Immunocompromised Children | Change in Lower Respiratory Tract Infection (LRI) Score During the Study | 6 doses | 0.1 units on a scale | Standard Deviation 0.3 |
| Immunocompromised Children | Change in Lower Respiratory Tract Infection (LRI) Score During the Study | 7 doses | 0.0 units on a scale | Standard Deviation 0.2 |
| Immunocompromised Children | Change in Lower Respiratory Tract Infection (LRI) Score During the Study | 8 doses | 0.1 units on a scale | Standard Deviation 0.3 |
| Immunocompromised Children | Change in Lower Respiratory Tract Infection (LRI) Score During the Study | 9 doses | 0.0 units on a scale | Standard Deviation 0 |
Secondary
Mean Duration of Respiratory Support
The presence/absence of respiratory support (oxygen therapy, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure, and other mechanical respiratory support or Intensive Care Unit admission) and the start and end dates of respiratory support were documented on the case report form (CRF).
Time frame: From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Population: Participants with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immunocompromised Children | Mean Duration of Respiratory Support | 40.0 days | Standard Deviation 62.4 |
Secondary
Mean Hospitalization Length Due to Respiratory Syncytial Virus (RSV) Infection
The date of hospitalization due to RSV infection and the date of hospital discharge were documented on the case report form (CRF).
Time frame: From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Population: Participants with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immunocompromised Children | Mean Hospitalization Length Due to Respiratory Syncytial Virus (RSV) Infection | 9.5 days | Standard Deviation 2.1 |
Secondary
Number of Hospitalized Participants Requiring Respiratory Support
The presence/absence of respiratory support, (oxygen therapy, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure, and other mechanical respiratory support or Intensive Care Unit admission) the start and end dates of respiratory support, and the dates of hospitalization and discharge were documented on the case report form (CRF).
Time frame: From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Population: Participants with available data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunocompromised Children | Number of Hospitalized Participants Requiring Respiratory Support | 1 Participants |
Secondary
Number of Participants Hospitalized Due to Respiratory Syncytial Virus (RSV) Infection
Hospitalization due to RSV infection or the presence/absence of positive RSV antigen test results during hospitalization was documented on the case report form (CRF).
Time frame: From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Population: Participants with available data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunocompromised Children | Number of Participants Hospitalized Due to Respiratory Syncytial Virus (RSV) Infection | 2 Participants |