Pulmonary Arterial Hypertension
Conditions
Brief summary
The Thelin Patient Safety Registry is a post-marketing program in the European Union (EU) that is designed to supplement the reporting of spontaneous adverse events (AE) and better characterize known and potential safety signals for Thelin. The registry is a secure, restricted access, electronic system which collects anonymous, pre-defined, patient-level data on demographic variables, safety monitoring measurements (i.e. liver function tests, haemoglobin and international normalized ratio (INR) measurements), concomitant medications, information on AEs and Thelin drug discontinuation. Regular review of the data is conducted to assess the frequency of identified safety risks and to monitor for the emergence of new safety signals at monthly pharmacovigilance meetings, quarterly signal detection meetings, and for each Periodic Safety Update Report (PSUR).
Detailed description
Non-probability sample
Interventions
Please note that this is a non-interventional study and no drug is actually given as an intervention. Instead, patients prescribed THELIN are being followed under real world circumstances. However at the request of the QA group at CT.gov, we were instructed to add sitaxentan sodium as the intervention type, regardless of the fact that this is a non-interventional study.
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of a personally signed and dated informed consent document by the patient indicating that he/she (or a legally acceptable representative) has been informed of all pertinent aspects of the study is a requirement for inclusion. * Additional inclusion criteria reflect the approved label for Thelin as outlined in the SmPC.
Exclusion criteria
* There are no specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Elevated Liver Function Post-baseline | Monthly up to 1 year | Elevated liver function: greater than 3 times the upper limit of normal (\>3 x ULN) alanine aminotransferase (ALT) and aspartase aminotransferase (AST) levels. Laboratory data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analyses. |
| Percentage of Participants With a Decrease in Hemoglobin Post-baseline | Monthly up to 1 year | Laboratory data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analyses. |
| Percentage of Participants With Increases in Total, Conjugated and Non-conjugated Bilirubin Post-baseline | Monthly up to 1 year | Total and conjugated bilirubin levels measured from blood, but indirect bilirubin calculated. Indirect bilirubin=Total bilirubin - Conjugated bilirubin. Laboratory data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analyses. |
| Duration of Exposure to Thelin | 1 Year | Time between the first and last dose of Thelin. For participants who continued Thelin from TOPS (another study), the initial TOPS' Thelin start date was used. |
| Adverse Events (AEs) by Seriousness and Relationship to Treatment | Baseline up to year 1 | Counts of participants who had AEs or treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Serious adverse events (SAEs) were reported from the time of informed consent. Relatedness to Thelin was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. |
| Clinical Status Since Last Visit | Monthly up to 1 year | Clinical status determined by status of pulmonary arterial hypertension (PAH) since last visit, reported as PAH remained stable, improved or deteriorated. |
| Concomitant Medications | Baseline, monthly up to 1 year | Number of participants with concomitant medication usage reported by drug categories. |
| Bleeding AEs by Seriousness, Relationship to Treatment, Endothelin-A Receptor Antagonist (ERA) Usage, and International Normalized Ratio (INR) Results | Baseline up to year 1 | Counts of participants who had bleeding events or treatment-emergent bleeding events, defined as newly occurring or worsening after first dose. Serious bleeding events reported from time of informed consent. Relatedness to Thelin assessed by investigator (Yes/No). ERA usage: was participant taking Vitamin K antagonist? (Yes/No). INR: participant's prothrombin time (PT) ratio. Participants with multiple occurrences of an AE within a category were counted once within the category. |
| Percentage of Participants Who Experienced Pulmonary Edema With the Presence of Veno-occlusive Disease | Baseline up to year 1 | The criteria used to determine whether participants had both pulmonary edema and veno-occlusive disease was at the discretion of the Investigator. |
Countries
Belgium, France, Germany
Participant flow
Recruitment details
The Sitaxentan Sodium program was discontinued December 10, 2010.
Participants by arm
| Arm | Count |
|---|---|
| Thelin Registry Patients The use and dosage recommendations for Thelin (sitaxentan sodium) was in accordance with the local summary of Product Characteristics. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Early study termination | 52 |
Baseline characteristics
| Characteristic | Thelin Registry Patients |
|---|---|
| Age Continuous | 60.5 years STANDARD_DEVIATION 18.1 |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 54 |
| serious Total, serious adverse events | 6 / 54 |
Outcome results
Primary
Adverse Events (AEs) by Seriousness and Relationship to Treatment
Counts of participants who had AEs or treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Serious adverse events (SAEs) were reported from the time of informed consent. Relatedness to Thelin was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.
Time frame: Baseline up to year 1
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thelin Registry Patients | Adverse Events (AEs) by Seriousness and Relationship to Treatment | Any TEAE | 11 participants |
| Thelin Registry Patients | Adverse Events (AEs) by Seriousness and Relationship to Treatment | TEAE related to Thelin | 1 participants |
| Thelin Registry Patients | Adverse Events (AEs) by Seriousness and Relationship to Treatment | SAE | 6 participants |
| Thelin Registry Patients | Adverse Events (AEs) by Seriousness and Relationship to Treatment | SAE related to Thelin | 1 participants |
Primary
Bleeding AEs by Seriousness, Relationship to Treatment, Endothelin-A Receptor Antagonist (ERA) Usage, and International Normalized Ratio (INR) Results
Counts of participants who had bleeding events or treatment-emergent bleeding events, defined as newly occurring or worsening after first dose. Serious bleeding events reported from time of informed consent. Relatedness to Thelin assessed by investigator (Yes/No). ERA usage: was participant taking Vitamin K antagonist? (Yes/No). INR: participant's prothrombin time (PT) ratio. Participants with multiple occurrences of an AE within a category were counted once within the category.
Time frame: Baseline up to year 1
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thelin Registry Patients | Bleeding AEs by Seriousness, Relationship to Treatment, Endothelin-A Receptor Antagonist (ERA) Usage, and International Normalized Ratio (INR) Results | Any bleeding event | 1 participants |
| Thelin Registry Patients | Bleeding AEs by Seriousness, Relationship to Treatment, Endothelin-A Receptor Antagonist (ERA) Usage, and International Normalized Ratio (INR) Results | Bleeding event related to Thelin | 0 participants |
| Thelin Registry Patients | Bleeding AEs by Seriousness, Relationship to Treatment, Endothelin-A Receptor Antagonist (ERA) Usage, and International Normalized Ratio (INR) Results | Serious bleeding event | 0 participants |
| Thelin Registry Patients | Bleeding AEs by Seriousness, Relationship to Treatment, Endothelin-A Receptor Antagonist (ERA) Usage, and International Normalized Ratio (INR) Results | Serious bleeding event related to Thelin | 0 participants |
| Thelin Registry Patients | Bleeding AEs by Seriousness, Relationship to Treatment, Endothelin-A Receptor Antagonist (ERA) Usage, and International Normalized Ratio (INR) Results | Bleeding event with ERA usage | 0 participants |
| Thelin Registry Patients | Bleeding AEs by Seriousness, Relationship to Treatment, Endothelin-A Receptor Antagonist (ERA) Usage, and International Normalized Ratio (INR) Results | Bleeding event with INR results | 0 participants |
Primary
Clinical Status Since Last Visit
Clinical status determined by status of pulmonary arterial hypertension (PAH) since last visit, reported as PAH remained stable, improved or deteriorated.
Time frame: Monthly up to 1 year
Population: Data not summarized due to the small number of participants in database.
Primary
Concomitant Medications
Number of participants with concomitant medication usage reported by drug categories.
Time frame: Baseline, monthly up to 1 year
Population: Data not summarized due to the small number of participants in database.
Primary
Duration of Exposure to Thelin
Time between the first and last dose of Thelin. For participants who continued Thelin from TOPS (another study), the initial TOPS' Thelin start date was used.
Time frame: 1 Year
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thelin Registry Patients | Duration of Exposure to Thelin | 21.5 months | Standard Deviation 15.3 |
Primary
Percentage of Participants Who Experienced Pulmonary Edema With the Presence of Veno-occlusive Disease
The criteria used to determine whether participants had both pulmonary edema and veno-occlusive disease was at the discretion of the Investigator.
Time frame: Baseline up to year 1
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thelin Registry Patients | Percentage of Participants Who Experienced Pulmonary Edema With the Presence of Veno-occlusive Disease | 0 percentage of participants |
Primary
Percentage of Participants With a Decrease in Hemoglobin Post-baseline
Laboratory data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analyses.
Time frame: Monthly up to 1 year
Population: Data not summarized due to the small number of participants in database.
Primary
Percentage of Participants With Elevated Liver Function Post-baseline
Elevated liver function: greater than 3 times the upper limit of normal (\>3 x ULN) alanine aminotransferase (ALT) and aspartase aminotransferase (AST) levels. Laboratory data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analyses.
Time frame: Monthly up to 1 year
Population: Full Analysis Set (FAS): participants enrolled in Patient Registry of Sitaxentan in Europe (PROSE). Number of participants analyzed (N): participants with evaluable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thelin Registry Patients | Percentage of Participants With Elevated Liver Function Post-baseline | ALT >3 xULN | 2.2 percentage of participants |
| Thelin Registry Patients | Percentage of Participants With Elevated Liver Function Post-baseline | AST >3 xULN | 2.2 percentage of participants |
Primary
Percentage of Participants With Increases in Total, Conjugated and Non-conjugated Bilirubin Post-baseline
Total and conjugated bilirubin levels measured from blood, but indirect bilirubin calculated. Indirect bilirubin=Total bilirubin - Conjugated bilirubin. Laboratory data were analyzed by several local laboratories. There were subtle differences in the reference ranges used for analyses.
Time frame: Monthly up to 1 year
Population: Data not summarized due to the small number of participants in database.