Trial Outcomes & Findings for Study of Incidence of Respiratory Tract AEs in Patients Treated With Tyvaso® Compared to Other FDA Approved PAH Therapies (NCT NCT01266265)

Last Updated: 2016-02-17

Results Overview

Percentage of patients who experienced a respiratory tract-related adverse event (grouped by category of interest) during the study.

Recruitment status

COMPLETED

Target enrollment

1333 participants

Primary outcome timeframe

Follow-up every 3 months

Results posted on

2016-02-17

Participant Flow

The recruitment period for this study was February 2010 to December 2014. All sites were located in the United States.

Participant milestones

Participant milestones
Measure	Tyvaso The Tyvaso group will consist of patients receiving Tyvaso and may be receiving another FDA approved PAH therapy as part of routine care. inhaled prostacyclin: Tyvaso	Control The control group will consist of patients with no previous Tyvaso exposure and not taking Tyvaso at the time of Baseline visit, but treated with any other FDA approved PAH therapy as part of routine care. inhaled prostacyclin: As prescribed by the physician prostacyclin: As prescribed by the physician subcutaneous and intravenous prostacyclin: As prescribed by physician oral ERA: As prescribed by physician oral PDE5 inhibitors: As prescribed by physician
Overall Study STARTED	666	667
Overall Study COMPLETED	461	477
Overall Study NOT COMPLETED	205	190

Reasons for withdrawal

Reasons for withdrawal
Measure	Tyvaso The Tyvaso group will consist of patients receiving Tyvaso and may be receiving another FDA approved PAH therapy as part of routine care. inhaled prostacyclin: Tyvaso	Control The control group will consist of patients with no previous Tyvaso exposure and not taking Tyvaso at the time of Baseline visit, but treated with any other FDA approved PAH therapy as part of routine care. inhaled prostacyclin: As prescribed by the physician prostacyclin: As prescribed by the physician subcutaneous and intravenous prostacyclin: As prescribed by physician oral ERA: As prescribed by physician oral PDE5 inhibitors: As prescribed by physician
Overall Study Death	95	73
Overall Study Lost to Follow-up	23	28
Overall Study Withdrawal by Subject	13	11
Overall Study Respiratory-related adverse event	2	1
Overall Study Transferred care to another provider	22	28
Overall Study Stopped/changed PAH medication(s)	16	9
Overall Study Enrolled in another clinical study	15	26
Overall Study Non-compliance	8	5
Overall Study Lung transplant	6	5
Overall Study Site closed early	4	3
Overall Study Clinical worsening	1	1

Baseline Characteristics

Study of Incidence of Respiratory Tract AEs in Patients Treated With Tyvaso® Compared to Other FDA Approved PAH Therapies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tyvaso n=666 Participants The Tyvaso group will consist of patients receiving Tyvaso and may be receiving another FDA approved PAH therapy as part of routine care. inhaled prostacyclin: Tyvaso	Control n=667 Participants The control group will consist of patients with no previous Tyvaso exposure and not taking Tyvaso at the time of the Baseline visit, but receiving any other FDA approved PAH therapy as part of routine care.	Total n=1333 Participants Total of all reporting groups
Age, Continuous	57.5 years n=5 Participants	57.0 years n=7 Participants	57.25 years n=5 Participants
Sex: Female, Male Female	519 Participants n=5 Participants	532 Participants n=7 Participants	1051 Participants n=5 Participants
Sex: Female, Male Male	147 Participants n=5 Participants	135 Participants n=7 Participants	282 Participants n=5 Participants
Disease etiology Idiopathic/heritable/drug- or toxin-induced	341 participants n=5 Participants	389 participants n=7 Participants	730 participants n=5 Participants
Disease etiology Connective tissue disease	223 participants n=5 Participants	195 participants n=7 Participants	418 participants n=5 Participants
Disease etiology Congential heart disease	55 participants n=5 Participants	37 participants n=7 Participants	92 participants n=5 Participants
Disease etiology HIV infection/porto-pulmonary	53 participants n=5 Participants	55 participants n=7 Participants	108 participants n=5 Participants
Disease etiology Other	9 participants n=5 Participants	4 participants n=7 Participants	13 participants n=5 Participants
Race White	483 participants n=5 Participants	510 participants n=7 Participants	993 participants n=5 Participants
Race Black/African American	116 participants n=5 Participants	107 participants n=7 Participants	223 participants n=5 Participants
Race Other/race not disclosed	42 participants n=5 Participants	33 participants n=7 Participants	75 participants n=5 Participants
Race Asian	21 participants n=5 Participants	15 participants n=7 Participants	36 participants n=5 Participants
Race Native Hawaiian/Pacific Islander	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Race American Indian/Alaska Native	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Years Since PAH Diagnosis	2.9 years n=5 Participants	2.9 years n=7 Participants	2.9 years n=5 Participants
Baseline PAH Medication Tyvaso (treprostinil) inhalation	666 participants n=5 Participants	0 participants n=7 Participants	666 participants n=5 Participants
Baseline PAH Medication Remodulin (treprostinil)	2 participants n=5 Participants	150 participants n=7 Participants	152 participants n=5 Participants
Baseline PAH Medication Flolan (epoprostenol)	2 participants n=5 Participants	44 participants n=7 Participants	46 participants n=5 Participants
Baseline PAH Medication Veletri (epoprostinol)	0 participants n=5 Participants	36 participants n=7 Participants	36 participants n=5 Participants
Baseline PAH Medication Ventavis (iloprost) inhalation	0 participants n=5 Participants	33 participants n=7 Participants	33 participants n=5 Participants
Baseline PAH Medication Revatio (sildenafil citrate)	294 participants n=5 Participants	236 participants n=7 Participants	530 participants n=5 Participants
Baseline PAH Medication Adcirca (tadalafil)	239 participants n=5 Participants	224 participants n=7 Participants	463 participants n=5 Participants
Baseline PAH Medication Letairis (ambrisentan)	250 participants n=5 Participants	200 participants n=7 Participants	450 participants n=5 Participants
Baseline PAH Medication Tracleer (bosentan)	164 participants n=5 Participants	203 participants n=7 Participants	367 participants n=5 Participants
Baseline PAH Medication Opsumit (macitentan)	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Baseline PAH Medication Adempas (riociguat)	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants

PRIMARY outcome

Timeframe: Follow-up every 3 months

Percentage of patients who experienced a respiratory tract-related adverse event (grouped by category of interest) during the study.

Outcome measures

Outcome measures
Measure	Tyvaso n=666 Participants The Tyvaso group will consist of patients receiving Tyvaso and may be receiving another FDA approved PAH therapy as part of routine care. inhaled prostacyclin: Tyvaso	Control n=667 Participants The control group will consist of patients with no previous Tyvaso exposure and not taking Tyvaso at the time of the Baseline visit, but receiving any other FDA approved PAH therapy as part of routine care.
Prevalence of Respiratory Tract-Related Adverse Events of Interest Any Event	52 percentage of participants	51 percentage of participants
Prevalence of Respiratory Tract-Related Adverse Events of Interest Bleeding from the upper or lower respiratory tract	16 percentage of participants	14 percentage of participants
Prevalence of Respiratory Tract-Related Adverse Events of Interest Irritation/pain of nose, mouth, larynx, pharynx	17 percentage of participants	10 percentage of participants
Prevalence of Respiratory Tract-Related Adverse Events of Interest Upper or lower respiratory tract infection	37 percentage of participants	40 percentage of participants
Prevalence of Respiratory Tract-Related Adverse Events of Interest Wheezing, bronchospasm, or asthma/COPD exacerbate	12 percentage of participants	13 percentage of participants

Adverse Events

Tyvaso

Serious events: 96 serious events

Other events: 403 other events

Deaths: 0 deaths

Control

Serious events: 94 serious events

Other events: 388 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tyvaso n=666 participants at risk The Tyvaso group will consist of patients receiving Tyvaso and may be receiving another FDA approved PAH therapy as part of routine care. inhaled prostacyclin: Tyvaso	Control n=667 participants at risk The control group will consist of patients with no previous Tyvaso exposure and not taking Tyvaso at the time of the Baseline visit, but receiving any other FDA approved PAH therapy as part of routine care.
Respiratory, thoracic and mediastinal disorders Cough	18.3% 122/666 • Number of events 155 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	15.9% 106/667 • Number of events 119 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	14.9% 99/666 • Number of events 129 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	17.2% 115/667 • Number of events 158 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Epistaxis	13.4% 89/666 • Number of events 117 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	12.0% 80/667 • Number of events 109 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Bronchitis	8.6% 57/666 • Number of events 75 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	8.4% 56/667 • Number of events 73 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 55/666 • Number of events 63 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	9.9% 66/667 • Number of events 85 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Pneumonia	8.3% 55/666 • Number of events 62 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	8.1% 54/667 • Number of events 70 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Wheezing	7.5% 50/666 • Number of events 62 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	9.1% 61/667 • Number of events 81 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	6.6% 44/666 • Number of events 55 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	7.2% 48/667 • Number of events 63 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Sinusitis	6.2% 41/666 • Number of events 52 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	9.4% 63/667 • Number of events 73 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Throat irritation	5.9% 39/666 • Number of events 43 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	1.8% 12/667 • Number of events 13 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.6% 37/666 • Number of events 43 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	4.5% 30/667 • Number of events 32 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.9% 26/666 • Number of events 31 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.	5.5% 37/667 • Number of events 37 • Respiratory tract-related AEs were recorded from the time of informed consent to study completion or discontinuation. SAEs were included in the "Other" AE table because one participant may have experienced both an SAE and non-serious AE during the study. Non-respiratory-related AEs and SAEs were outside the scope of this study.

Additional Information

Nicole Leedom

United Therapeutics Corporation

Phone: 919-425-5870

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the United Therapeutics publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Publication restrictions are in place

Restriction type: OTHER