Pilot Chart Review Study Of Sitaxentan Sodium (Thelin) In Patients With Pulmonary Arterial Hypertension (PAH)

NON-INTERVENTIONAL (NI) DRUG STUDY PROTOCOL: THREE-COUNTRY PILOT STUDY FOR RETROSPECTIVE CHART REVIEW OF EFFECTIVENESS OF THELIN® (SITAXSENTAN) IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH)

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01445873

Enrollment

Registered

2011-10-04

Start date

2009-12-01

Completion date

2011-03-28

Last updated

2020-09-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary arterial hypertension, sitaxentan sodium, Thelin

Brief summary

The objectives of this study are to develop research methods and corresponding materials for a study of the effectiveness of sitaxentan sodium (Thelin) in real-world settings; to pilot test these methods at three study centers in Europe; and to refine and finalize research methods and corresponding materials for possible use in a follow-on, full-scale examination of the effectiveness of sitaxentan sodium (Thelin) in real-world settings.

Detailed description

At each centre, approximately 12-15 Pulmonary Arterial Hypertension (PAH) consecutive patients who have received Thelin and who meet all other study entry criteria.

Interventions

DRUGSitaxentan sodium

Sitaxentan sodium 100 mg / day

Study design

Observational model

COHORT

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Idiopathic PAH, or PAH secondary to connective tissue disease * Receipt of Thelin for treatment of PAH * 6 months of follow-up (except in the event of death) subsequent to initial receipt of Thelin * Minimum of one clinic visit documented in the medical record during the 6-month period subsequent to initial receipt of Thelin

Exclusion criteria

* Participation in any investigational study of Thelin or any other medication for the treatment of PAH during the period beginning 6 months prior to initial receipt of Thelin and ending 6 months subsequent to such receipt * Receipt of Thelin prior to January 11, 2005 (i.e., the date following the last day on which patients could be enrolled in double-blind treatment in STRIDE-1, STRIDE-2, and/or STRIDE-6); or * Known contraindications to Thelin therapy (i.e., known hypersensitivity to sitaxsentan or any of its excipients; mild-to-severe hepatic impairment \[Child-Pugh Class A-C\]; elevated aminotransferases prior to initiation of treatment, defined as aspartate aminotransferase \[AST\] and/or alanine aminotransferase \[ALT\] \>3 times upper limit of normal \[ULN\]; concomitant use of cyclosporin A; lactation)

Design outcomes

Primary

Measure	Time frame	Description
Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Mean Time to Therapy Augmentation	Day 1 to Month 6	Participants still receiving Thelin with evidence of receipt of another PAH-related therapy (eg. bosentan, sildenafil) not previously received during the study period. Mean time in months to therapy augmentation.
Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Therapy Switching	Day 1 to Month 6	Participants with evidence of discontinuation of Thelin therapy and evidence of receipt of another PAH-related therapy not previously received during the study period.
Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Therapy Discontinuation	Day 1 to Month 6	Participants were designated as having discontinued Thelin therapy if there was evidence in the medical records that treatment had been terminated.
Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Therapy Duration	Day 1 to Month 6	Duration of Thelin therapy based on time from index date (Day 1 of treatment) until the date of discontinuation of Thelin therapy.
Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Numbers of Therapy-days Dispensed	Day 1 to Month 6	Duration of Thelin therapy from initial receipt until date of discontinuation of thelin therapy or the end of follow-up, whichever occurred first.
Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Daily Dosage	Day 1 to Month 6	Daily dosage of Thelin based on information in the medical record for the baseline visit and all follow-up clinic visits.

Secondary

Measure	Time frame	Description
Change From Baseline in Pulmonary Vascular Resistance	Baseline to Month 6	Difference between pre-index and follow-up value.
Change From Baseline in Cardiac Output	Baseline to Month 6	Difference between pre-index and follow-up value.
Change From Baseline in Tei Index	Baseline to Month 6	Difference between pre-index and follow-up value. Combined myocardial performance index calculated by adding isovolumic contraction time and isovolumic relaxation time and dividing the resulting sum by ejection time.
Change From Baseline in Tricuspid Regurgitant Velocity	Baseline to Month 6	Difference between pre-index and follow-up value.
Change From Baseline in the Total Distance Walked During 6 Minute Walk Test (6MWT)	Baseline to Month 6	6MWT was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety. Difference between pre-index and follow-up value.
Change From Baseline in Borg Dyspnoea Score	Baseline to Month 6	Borg dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight \[just noticeable\]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe \[almost maximum\] and 10 (maximum). Difference between pre-index and follow-up value.
Use of Other Pulmonary Arterial Hypertension (PAH)-Related Medications	Day 1 to Month 6	Use of PAH-related medications other than Thelin described by class of agent received.
Pulmonary Arterial Hypertension (PAH) Severity and Functional Status: Time to Clinical Worsening	Day 1 to Month 6	Occurrence of any of the following: death, unplanned PAH-related hospitalization, initiation of epoprostenol, arterial septostomy, lung or heart/lung transplantation, ≥15% decrease from baseline in 6 minute walk test, signs/symptoms of right sided heart failure, and/or worsening WHO functional class.
Other Pulmonary Arterial Hypertension (PAH)-Related Outcomes: Mortality	Day 1 to Month 6	Number of participants who died during the follow-up period.
Number of Hospitalizations	Day 1 to Month 6	All hospitalizations during the follow-up period recorded in medical records.
Other Pulmonary Arterial Hypertension (PAH)-Related Outcomes: Lung Transplantation	Day 1 to Month 6	Number of participants who received an lung transplant during hospitalization.
Other Pulmonary Arterial Hypertension (PAH)-Related Outcomes: Heart/Lung Transplantation	Day 1 to Month 6	Number of participants who received an heart/lung transplant during hospitalization.
Other Pulmonary Arterial Hypertension (PAH)-Related Outcomes: Atrial Septostomy	Day 1 to Month 6	Number of participants who received an atrial septostomy (balloon or blade) during hospitalization.
Change From Baseline in Percent of Predicted Peak VO2	Baseline to Month 6	Difference between pre-index and follow-up value.
Change From Baseline in World Health Organization (WHO) Functional Class of Pulmonary Hypertension	Baseline to Month 6	Class I: no limitation of usual (usl) physical activity (PA); PA does not increase(d) (incr) dyspnea (dys), fatigue (ftg), chest pain (CP), or syncope (syn); Class II: mild limitation of usl PA; no discomfort at rest, but normal PA causes incr dys, ftg, CP, or presyncope (presyn); Class III: marked limitation of PA; no discomfort at rest but \< ordinary activity causes incr dys, ftg, CP, or presyn; Class IV: unable to perform any PA at rest; may have signs of right ventricular failure; sys and/or ftg at rest and symptoms are incr by almost any PA.
Change From Baseline in Mean Right Atrial Pressure	Baseline to Month 6	Difference between pre-index and follow-up value.
Change From Baseline in Mean Pulmonary Artery Pressure	Baseline to Month 6	Difference between pre-index and follow-up value.
Change From Baseline in Pulmonary Capillary Wedge Pressure	Baseline to Month 6	Difference between pre-index and follow-up value.
Change From Baseline in Left Ventricular End Diastolic Pressure	Baseline to Month 6	Difference between pre-index and follow-up value.

Participant flow

Recruitment details

Data for this retrospective non-interventional study were abtracted from the medical records of subjects who met study entry criteria.

Pre-assignment details

Patterns of treatment with Thelin including duration and daily dosages reflect treament participants received in clinical practice. Treatment was not specified by the protocol.

Participants by arm

Arm	Count
Sitaxentan (Thelin) Duration and dose as prescribed in clinical practice.	36
Total	36

Baseline characteristics

Characteristic	Sitaxentan (Thelin)
Age, Customized 19 to 24 years	0 Participants
Age, Customized 25 to 30 years	2 Participants
Age, Customized 31 to 36 years	2 Participants
Age, Customized 37 to 42 years	1 Participants
Age, Customized 43 to 48 years	2 Participants
Age, Customized 49 to 54 years	4 Participants
Age, Customized 55 to 60 years	2 Participants
Age, Customized 61 to 66 years	5 Participants
Age, Customized 67 to 72 years	9 Participants
Age, Customized 73 to 78 years	7 Participants
Age, Customized 79 to 84 years	1 Participants
Age, Customized 85 to 90 years	1 Participants
Sex: Female, Male Female	29 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	27 / 36
serious Total, serious adverse events	0 / 36

Outcome results

Primary

Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Daily Dosage

Daily dosage of Thelin based on information in the medical record for the baseline visit and all follow-up clinic visits.

Time frame: Day 1 to Month 6

Population: FAS

Arm	Measure	Value (MEAN)
Sitaxentan (Thelin)	Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Daily Dosage	100.0 mg

Primary

Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Mean Time to Therapy Augmentation

Participants still receiving Thelin with evidence of receipt of another PAH-related therapy (eg. bosentan, sildenafil) not previously received during the study period. Mean time in months to therapy augmentation.

Time frame: Day 1 to Month 6

Population: Full analysis set (FAS): participants with idiopathic pulmonary arterial hypertension (PAH) or PAH secondary to connective tissue disease, receipt of Thelin for treatment of PAH, 6 months of follow-up (except for death) after initial receipt (IR) of Thelin, and at least 1 clinic visit in medical record during 6-month period after IR of Thelin.

Arm	Measure	Value (MEAN)	Dispersion
Sitaxentan (Thelin)	Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Mean Time to Therapy Augmentation	2.2 months	Standard Deviation 1.2

Primary

Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Numbers of Therapy-days Dispensed

Duration of Thelin therapy from initial receipt until date of discontinuation of thelin therapy or the end of follow-up, whichever occurred first.

Time frame: Day 1 to Month 6

Population: Not analyzed: duration of Thelin therapy as number of therapy days dispensed was not summarized; this measure was reported as duration in months only.

Primary

Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Therapy Discontinuation

Participants were designated as having discontinued Thelin therapy if there was evidence in the medical records that treatment had been terminated.

Time frame: Day 1 to Month 6

Population: FAS

Arm	Measure	Value (NUMBER)
Sitaxentan (Thelin)	Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Therapy Discontinuation	0 participants

Primary

Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Therapy Duration

Duration of Thelin therapy based on time from index date (Day 1 of treatment) until the date of discontinuation of Thelin therapy.

Time frame: Day 1 to Month 6

Population: FAS; participants without evidence of discontinuation of Thelin therapy were censored at the end of follow-up (at 6 months or death if prior to 6 months).

Arm	Measure	Value (MEAN)	Dispersion
Sitaxentan (Thelin)	Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Therapy Duration	6 months	Standard Deviation 0

Primary

Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Therapy Switching

Participants with evidence of discontinuation of Thelin therapy and evidence of receipt of another PAH-related therapy not previously received during the study period.

Time frame: Day 1 to Month 6

Population: FAS

Arm	Measure	Value (NUMBER)
Sitaxentan (Thelin)	Patterns of Pharmacotherapy With Sitaxentan Sodium (Thelin): Therapy Switching	0 participants

Secondary

Change From Baseline in Borg Dyspnoea Score

Borg dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight \[just noticeable\]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe \[almost maximum\] and 10 (maximum). Difference between pre-index and follow-up value.