Pulmonary Hypertension
Conditions
Brief summary
The objective of this surveillance is to collect information about 1) adverse drug reaction not expected from the LPD (unknown adverse drug reaction), 2) the incidence of adverse drug reactions in this surveillance, and 3)factors considered to affect the safety and/or efficacy of this drug.
Detailed description
All the patients whom an investigator prescribes the first SILDENAFIL(Revatio) should be registered consecutively until the number of subjects reaches target number in order to extract patients enrolled into the investigation at random.
Interventions
DRUGSILDENAFIL
Revatio® Tablets 20 mg Dosage, Frequency: According to Japanese LPD, For oral use, the adult dose is 20 mg three times a day. Duration: According to the protocol of A1481263, the duration of the investigation for findings regarding safety and efficacy of a patient is from the first drug administration to the 3 years after the first administration.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
0 Days to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients need to be administered SILDENAFIL(Revatio) in order to be enrolled in the surveillance.
Exclusion criteria
* Patients not administered SILDENAFIL(Revatio).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Related Adverse Events | 3 years | A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to sildenafil citrate was assessed by the physician/investigator. |
| Number of Participants With Treatment-Related Adverse Events Unexpected From Japanese Package Insert | 3 years | A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Expectedness of the adverse event was determined according to the Japanese package insert. Relatedness to sildenafil citrate was assessed by the physician/investigator. |
| Number of Paritcipants With Treatment-Related Adverse Events by Age | 3 years | A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Relatedness to sildenafil citrate was assessed by the physician/investigator. Participants with treatment related adverse events were counted by age to assess whether it was risk factor for the treatment related adverse events. |
| Number of Paritcipants With Treatment-Related Adverse Events by Gender | 3 years | A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Relatedness to sildenafil citrate was assessed by the physician/investigator. Participants with treatment related adverse events were counted by gender to assess whether it was risk factor for the treatment related adverse events. |
| Number of Participants With Treatment-Related Adverse Events by Disease Type | 3 years | A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Relatedness to sildenafil citrate was assessed by the physician/investigator. Participants with treatment related adverse events were counted by disease type to assess whether it was risk factor for the treatment related adverse events. \* indicates Associated Pulmonary Arterial Hypertension (APAH). \*\* refers to Pulmonary Veno Occlusive Disease/Pulmonary Capillary Hemangiomatosis. |
| Number of Participants With Treatmnt-Related Adverse Events by WHO Functional Classification of Severity | 3 years | A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Relatedness to sildenafil citrate was assessed by the physician/investigator. Participants with treatment related adverse events were counted by severity (WHO functional classification for PAH range;This system grades PAH severity according to the functional status of the patient. The grades range from Functional Class (FC) I, where the patient's disease does not affect their day-to-day activities, to FC IV, where patients are severely functionally impaired, even at rest. This functional classification system links symptoms with activity limitations, and allows clinicians to quickly predict disease progression and prognosis, as well as the need for specific treatment regimens, irrespective of the underlying etiology of PAH) to assess whether it was risk factor for the treatment related adverse events. |
| Clinical Efficacy Rate by Age | 3 years | Clinical effectiveness rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assessable effectiveness analysis population, was presented. Clinical effectiveness of sildenafil citrate was assessed as effective, ineffective or unassessable by the physician/investigator. Overall effectiveness of sildenafil citrate was determined by the physician/investigator based on clinical symptoms, laboratory values, and other examinations such as echocardiogram. Participants achieved clinical effectiveness by age were counted to assess whether it contributes to the clinical effectiveness. |
| Clinical Efficacy Rate by Gender | 3 years | Clinical effectiveness rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assessable effectiveness analysis population, was presented. Clinical effectiveness of sildenafil citrate was assessed as effective, ineffective or unassessable by the physician/investigator. Overall effectiveness of sildenafil citrate was determined by the physician/investigator based on clinical symptoms, laboratory values, and other examinations such as echocardiogram. Participants achieved clinical effectiveness by gender were counted to assess whether it contributes to the clinical effectiveness. |
| Clinical Efficacy Rate by Disease Type | 3 years | Clinical effectiveness rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assessable effectiveness analysis population, was presented. Clinical effectiveness of sildenafil citrate was assessed as effective, ineffective or unassessable by the physician/investigator. Overall effectiveness of sildenafil citrate was determined by the physician/investigator based on clinical symptoms, laboratory values, and other examinations such as echocardiogram. Participants achieved clinical effectiveness by disease type were counted to assess whether it contributes to the clinical effectiveness. \* indicates Associated Pulmonary Arterial Hypertension (APAH). \*\* refers to Pulmonary Veno Occlusive Disease/Pulmonary Capillary Hemangiomatosis. |
| Clinical Efficacy Rate by WHO Functional Classificaton of Severity | 3 years | Clinical effectiveness rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assessable effectiveness analysis population, was presented. Clinical effectiveness of sildenafil citrate was assessed as effective, ineffective or unassessable by the physician/investigator. Overall effectiveness of sildenafil citrate was determined by the physician/investigator based on clinical symptoms, laboratory values, and other examinations such as echocardiogram. Participants achieved clinical effectiveness by severity (WHO functional classification of PAH;The grades range from Functional Class (FC) I, where the patient's disease does not affect their day-to-day activities, to FC IV, where patients are severely functionally impaired, even at rest. This functional classification system links) were counted to assess whether it contributes to the clinical effectiveness. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Revatio (Sildenafil Citrate) Participants who received Revaio (Sildenafil citrate) as indicated in the approved local product document were observed for a period of 3 years. The dosage can be adjusted as per physician's discretion. | 3,304 |
| Total | 3,304 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | No Drug Administration | 4 |
| Overall Study | No Visit After First Day of Treatment | 13 |
| Overall Study | Protocol Violation | 10 |
| Overall Study | Safety Not Assessable | 6 |
Baseline characteristics
| Characteristic | Revatio (Sildenafil Citrate) |
|---|---|
| Age, Customized ≥15 years | 2254 Participants |
| Age, Customized ˂15 years | 1050 Participants |
| Age, Customized ≥65 years | 898 Participants |
| Age, Customized ˂65 years | 2406 Participants |
| Disease Type Collagen Vascular Disease* | 666 Participants |
| Disease Type Congenital Systemic to Pulmonary Shunts* | 985 Participants |
| Disease Type Idiopathic/Familial PAH (IPAH/FPAH) | 745 Participants |
| Disease Type Other PAH (Portal Hypertention/HIV Infection etc.) | 139 Participants |
| Disease Type Other Than PAH | 665 Participants |
| Disease Type Persistent PH of the Newborn (PPHN) | 59 Participants |
| Disease Type PVOD/PCH** | 44 Participants |
| Disease Type Unknown | 1 Participants |
| Sex/Gender, Customized Female | 2057 Participants |
| Sex/Gender, Customized Male | 1247 Participants |
| WHO Functional Classification of PAH Class I | 344 Participants |
| WHO Functional Classification of PAH Class II | 1012 Participants |
| WHO Functional Classification of PAH Class III | 1279 Participants |
| WHO Functional Classification of PAH Class IV | 545 Participants |
| WHO Functional Classification of PAH Not Classified | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 509 / 3,304 |
| serious Total, serious adverse events | 982 / 3,304 |
Outcome results
Primary
Clinical Efficacy Rate by Age
Clinical effectiveness rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assessable effectiveness analysis population, was presented. Clinical effectiveness of sildenafil citrate was assessed as effective, ineffective or unassessable by the physician/investigator. Overall effectiveness of sildenafil citrate was determined by the physician/investigator based on clinical symptoms, laboratory values, and other examinations such as echocardiogram. Participants achieved clinical effectiveness by age were counted to assess whether it contributes to the clinical effectiveness.
Time frame: 3 years
Population: The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (overall evaluation by the physician/investigator based upon change in clinical symptoms and laboratory findings) at least once. Participants with observed effectiveness data were included in table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Age | ˂15 years (n=1049) | 72.0 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Age | ≥15 years (n=2252) | 62.0 Percentage of Participants |
Primary
Clinical Efficacy Rate by Disease Type
Clinical effectiveness rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assessable effectiveness analysis population, was presented. Clinical effectiveness of sildenafil citrate was assessed as effective, ineffective or unassessable by the physician/investigator. Overall effectiveness of sildenafil citrate was determined by the physician/investigator based on clinical symptoms, laboratory values, and other examinations such as echocardiogram. Participants achieved clinical effectiveness by disease type were counted to assess whether it contributes to the clinical effectiveness. \* indicates Associated Pulmonary Arterial Hypertension (APAH). \*\* refers to Pulmonary Veno Occlusive Disease/Pulmonary Capillary Hemangiomatosis.
Time frame: 3 years
Population: The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (overall evaluation by the physician/investigator based upon change in clinical symptoms and laboratory findings) at least once. Participants with observed effectiveness data were included in table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Disease Type | Other PAH (n=139) | 67.6 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Disease Type | Unknown (n=1) | 100.0 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Disease Type | Idiopathic/Familial PAH(IPAH/FPAH) (n=743) | 67.6 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Disease Type | Collagen Vascular Disease* (n=666) | 61.6 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Disease Type | Congenital Systemic to Pulmonary Shunts* (n=984) | 72.9 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Disease Type | PVOD/PCH** (n=44) | 40.9 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Disease Type | Persistent PH of the Newborn (PPHN) (n=59) | 55.9 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Disease Type | Other Than PAH (n=665) | 56.5 Percentage of Participants |
Primary
Clinical Efficacy Rate by Gender
Clinical effectiveness rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assessable effectiveness analysis population, was presented. Clinical effectiveness of sildenafil citrate was assessed as effective, ineffective or unassessable by the physician/investigator. Overall effectiveness of sildenafil citrate was determined by the physician/investigator based on clinical symptoms, laboratory values, and other examinations such as echocardiogram. Participants achieved clinical effectiveness by gender were counted to assess whether it contributes to the clinical effectiveness.
Time frame: 3 years
Population: The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (overall evaluation by the physician/investigator based upon change in clinical symptoms and laboratory findings) at least once. Participants with observed effectiveness data were included in table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Gender | Female (n=2054) | 65.9 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by Gender | Male (n=1247) | 64.0 Percentage of Participants |
Primary
Clinical Efficacy Rate by WHO Functional Classificaton of Severity
Clinical effectiveness rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assessable effectiveness analysis population, was presented. Clinical effectiveness of sildenafil citrate was assessed as effective, ineffective or unassessable by the physician/investigator. Overall effectiveness of sildenafil citrate was determined by the physician/investigator based on clinical symptoms, laboratory values, and other examinations such as echocardiogram. Participants achieved clinical effectiveness by severity (WHO functional classification of PAH;The grades range from Functional Class (FC) I, where the patient's disease does not affect their day-to-day activities, to FC IV, where patients are severely functionally impaired, even at rest. This functional classification system links) were counted to assess whether it contributes to the clinical effectiveness.
Time frame: 3 years
Population: The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (overall evaluation by the physician/investigator based upon change in clinical symptoms and laboratory findings) at least once. Participants with observed effectiveness data were included in table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by WHO Functional Classificaton of Severity | Class I (n=344) | 76.2 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by WHO Functional Classificaton of Severity | Class II (n=1010) | 70.5 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by WHO Functional Classificaton of Severity | Class III (n=1279) | 64.2 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by WHO Functional Classificaton of Severity | Class IV (n=544) | 52.4 Percentage of Participants |
| Revatio (Sildenafil Citrate) | Clinical Efficacy Rate by WHO Functional Classificaton of Severity | Not Classified (n=124) | 57.3 Percentage of Participants |
Primary
Number of Paritcipants With Treatment-Related Adverse Events by Age
A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Relatedness to sildenafil citrate was assessed by the physician/investigator. Participants with treatment related adverse events were counted by age to assess whether it was risk factor for the treatment related adverse events.
Time frame: 3 years
Population: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received sildenafil citrate at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Revatio (Sildenafil Citrate) | Number of Paritcipants With Treatment-Related Adverse Events by Age | ˂15 years (n=1050) | 57 Paritcipants |
| Revatio (Sildenafil Citrate) | Number of Paritcipants With Treatment-Related Adverse Events by Age | ≥15 years (n=2254) | 391 Paritcipants |
Primary
Number of Paritcipants With Treatment-Related Adverse Events by Gender
A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Relatedness to sildenafil citrate was assessed by the physician/investigator. Participants with treatment related adverse events were counted by gender to assess whether it was risk factor for the treatment related adverse events.
Time frame: 3 years
Population: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received sildenafil citrate at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Revatio (Sildenafil Citrate) | Number of Paritcipants With Treatment-Related Adverse Events by Gender | Female (n=2057) | 323 Paritcipants |
| Revatio (Sildenafil Citrate) | Number of Paritcipants With Treatment-Related Adverse Events by Gender | Male (n=1247) | 125 Paritcipants |
Primary
Number of Participants With Treatment-Related Adverse Events
A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to sildenafil citrate was assessed by the physician/investigator.
Time frame: 3 years
Population: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received sildenafil citrate at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events | Treatment-Related Adverse Event | 448 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events | Treatment-Related Serious Adverse Event | 101 Participants |
Primary
Number of Participants With Treatment-Related Adverse Events by Disease Type
A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Relatedness to sildenafil citrate was assessed by the physician/investigator. Participants with treatment related adverse events were counted by disease type to assess whether it was risk factor for the treatment related adverse events. \* indicates Associated Pulmonary Arterial Hypertension (APAH). \*\* refers to Pulmonary Veno Occlusive Disease/Pulmonary Capillary Hemangiomatosis.
Time frame: 3 years
Population: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received sildenafil citrate at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events by Disease Type | Other PAH (n=139) | 25 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events by Disease Type | Other Than PAH (n=665) | 98 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events by Disease Type | Unkown (n=1) | 0 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events by Disease Type | Idiopathic/Familial PAH(IPAH/FPAH) (n=745) | 116 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events by Disease Type | Collagen Vascular Disease* (n=666) | 136 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events by Disease Type | Congenital Systemic to Pulmonary Shunts* (n=985) | 66 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events by Disease Type | PVOD/PCH** (n=44) | 4 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events by Disease Type | Persistent PH of the Newborn (PPHN) (n=59) | 3 Participants |
Primary
Number of Participants With Treatment-Related Adverse Events Unexpected From Japanese Package Insert
A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Expectedness of the adverse event was determined according to the Japanese package insert. Relatedness to sildenafil citrate was assessed by the physician/investigator.
Time frame: 3 years
Population: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received sildenafil citrate at least once.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Revatio (Sildenafil Citrate) | Number of Participants With Treatment-Related Adverse Events Unexpected From Japanese Package Insert | 196 Participants |
Primary
Number of Participants With Treatmnt-Related Adverse Events by WHO Functional Classification of Severity
A treatment-related adverse event was any untoward medical occurrence attributed to sildenafil citrate in a participant who received sildenafil citrate. Relatedness to sildenafil citrate was assessed by the physician/investigator. Participants with treatment related adverse events were counted by severity (WHO functional classification for PAH range;This system grades PAH severity according to the functional status of the patient. The grades range from Functional Class (FC) I, where the patient's disease does not affect their day-to-day activities, to FC IV, where patients are severely functionally impaired, even at rest. This functional classification system links symptoms with activity limitations, and allows clinicians to quickly predict disease progression and prognosis, as well as the need for specific treatment regimens, irrespective of the underlying etiology of PAH) to assess whether it was risk factor for the treatment related adverse events.
Time frame: 3 years
Population: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received sildenafil citrate at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Revatio (Sildenafil Citrate) | Number of Participants With Treatmnt-Related Adverse Events by WHO Functional Classification of Severity | Class I (n=344) | 34 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatmnt-Related Adverse Events by WHO Functional Classification of Severity | Class II (n=1012) | 127 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatmnt-Related Adverse Events by WHO Functional Classification of Severity | Class III (n=1279) | 204 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatmnt-Related Adverse Events by WHO Functional Classification of Severity | Class IV (n=545) | 63 Participants |
| Revatio (Sildenafil Citrate) | Number of Participants With Treatmnt-Related Adverse Events by WHO Functional Classification of Severity | Not Classified (n=124) | 20 Participants |