Imatinib (QTI571) in Pulmonary Arterial Hypertension | NCT00902174

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
imatinib mesylate	Experimental	Imatinib mesylate (QTI571) 200 mg once daily for two weeks, increased to 400 mg once daily if well tolerated. If 400 mg dose was not well tolerated, a down titration to 200 mg once daily was permitted.	Drug: imatinib mesylate
Placebo	Placebo Comparator	Placebo to imatinib mesylate taken once daily. Participants receiving placebo were allowed to receive already approved PAH treatments.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
imatinib mesylate	Drug	Two or 4 imatinib mesylate (QTI571) 100 mg film coated tablets once daily.	imatinib mesylate

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Difference in Six-minute Walk Distance Test (6MWD) Between Imatinib and Placebo at 24 Weeks	This standardized walk course was 30 meters in length. During the walk the participant was connected to a portable pulse oximeter via a finger probe. Participants were instructed to walk at a comfortable speed for as far as they could manage in 6 minutes. The total distance walked (in meters) was recorded. Results were compared between the 2 groups.	24 weeks

Secondary Outcomes

Measure	Description	Time Frame
Clinical Worsening Comparing Imatinib Versus Placebo for Adjudicated Cases	Clinical worsening per participant was measured by the onset of any adjudicated event (all cause mortality; overnight hospitalization for worsening of Pulmonary Arterial Hypertension (PAH); worsening of WHO functional class by one level; 15% decline in Six Minute Walk Distance (6MWD) measured on two consecutive occasions) at 24 weeks treatment, comparing imatinib to placebo groups. A cox regression analysis model was used.

Eligibility Module

Eligibility Criteria

Key Inclusion criteria

Male or female patients ≥18 years of age with a current diagnosis of pulmonary arterial hypertension (PAH) according to the Dana Point 2008 Meeting: World Health Organization (WHO) Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH following one year repair of congenital heart defect [Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD) or Posterior Descending Artery (PDA)], or PAH associated with diet therapies or other drugs
A Pulmonary Vascular Resistance (PVR) ≥ 800 dynes.sec.cm-5 (as assessed by Right Heart Catheterization (RHC) at screening or in the 3 months preceding the screening visit) despite treatment with two or more specific PAH therapies, including Endothelin Receptor Antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE5), or subcutaneous, inhaled, intravenous or oral prostacyclin analogues for ≥ 3 months. Background therapy doses were to be stable for ≥ 30 days except for warfarin and prostacyclin analogues ( ≥ 30 days but doses could vary even within the month before enrollment).
World Health Organization functional Class II-IV. For WHO Functional Class IV, one of the 2 or more specific PAH therapies were to be an inhaled, subcutaneous, intravenous or oral prostacyclin analogue, unless the subject showed intolerance of prostacyclin analogues.
6MWD ≥ 150 meters and ≤ 450 meters at screening. Distances of two consecutive 6MWTs were to be within 15% of one another.

Key Exclusion criteria

With a pulmonary capillary wedge pressure > 15 mm Hg to rule out PAH secondary to left ventricular dysfunction.
With a diagnosis of pulmonary artery or vein stenosis
Left ventricular ejection fraction (LVEF) < 45%
With Disseminated Intravascular Coagulation (DIC)
With evidence of major bleeding or intracranial hemorrhage
With a history of elevated intracranial pressure
With a history of latent bleeding risk such as diabetic retinopathy, gastrointestinal bleeding due to gastric or duodenal ulcers, or colitis ulcerosa
With a QTcF > 450 msec for males and > 470 msec for females at screening and baseline in the absence of right bundle branch block.
With a history of ventricular tachycardia, ventricular fibrillation or ventricular flutter
With a history of Torsades de Pointes
With a history of long QT syndrome
Having undergone atrial septostomy in the 3 months prior to the screening visit

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Birmingham	Alabama	35294	United States
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26514759	Derived	Querejeta Roca G, Campbell P, Claggett B, Solomon SD, Shah AM. Right Atrial Function in Pulmonary Arterial Hypertension. Circ Cardiovasc Imaging. 2015 Nov;8(11):e003521; discussion e003521. doi: 10.1161/CIRCIMAGING.115.003521.
25367310	Derived	Querejeta Roca G, Campbell P, Claggett B, Vazir A, Quinn D, Solomon SD, Shah AM. Impact of lowering pulmonary vascular resistance on right and left ventricular deformation in pulmonary arterial hypertension. Eur J Heart Fail. 2015 Jan;17(1):63-73. doi: 10.1002/ejhf.177. Epub 2014 Nov 4.

Label	URL
Related Info	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Imatinib Mesylate	Imatinib mesylate (QTI571) 200 mg once daily for two weeks, increased to 400 mg once daily if well tolerated. If 400 mg dose was not well tolerated, a down titration to 200 mg once daily was permitted.
FG001	Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Difference in Six-minute Walk Distance Test (6MWD) Between Imatinib and Placebo at 24 Weeks

This standardized walk course was 30 meters in length. During the walk the participant was connected to a portable pulse oximeter via a finger probe. Participants were instructed to walk at a comfortable speed for as far as they could manage in 6 minutes. The total distance walked (in meters) was recorded. Results were compared between the 2 groups.

The Full Analysis Set includes all participants who received at least one dose of study drug and completed the 6MWD Six-minute walk test at week 24. Repeated measurement model was used for this analysis.

Posted

Least Squares Mean

Standard Error

meters

24 weeks

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG00092 OG00193

Title

Denominators

Categories

Title	Measurements
	OG000382.94± 9.790 OG001351.18± 9.834

Secondary

Clinical Worsening Comparing Imatinib Versus Placebo for Adjudicated Cases

Clinical worsening per participant was measured by the onset of any adjudicated event (all cause mortality; overnight hospitalization for worsening of Pulmonary Arterial Hypertension (PAH); worsening of WHO functional class by one level; 15% decline in Six Minute Walk Distance (6MWD) measured on two consecutive occasions) at 24 weeks treatment, comparing imatinib to placebo groups. A cox regression analysis model was used.

The Full Analysis Set included all participants who received at least one dose of study drug and experienced an adjudicated event. A cox regression analysis model was used.

Posted

Number

percentage of participants

24 weeks

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Right Atrial Pressure

Change from baseline in right atrial pressure (mmHg) was measured via right heart catheterization according to the local hospital procedures. The right atrial pressure was assessed when the participant was in a stable hemodynamic rest state. A higher right atrial pressure number indicates worsening.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

mm Hg

baseline and week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Mean Pulmonary Arterial Pressure

Change from baseline in mean pulmonary arterial pressure (mmHg) was measured via right heart catheterization according to the local hospital procedures. The mean pulmonary arterial pressure was assessed when the participant was in a stable hemodynamic rest state. A higher mean pulmonary arterial pressure number indicates worsening.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis

Posted

Least Squares Mean

Standard Error

mm Hg

baseline and week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Mean Pulmonary Capillary Wedge Pressure

Change from baseline in mean pulmonary capillary wedge pressure (mmHg)was measured via right heart catheterization according to the local hospital procedures. The right atrial mean pulmonary capillary wedge pressure was assessed when the participant was in a stable hemodynamic rest state.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

mm Hg

baseline and week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Systemic Vascular Resistance

Change from baseline in systemic vascular resistance (dynes*sec*cm^-5) was measured via right heart catheterization according to the local hospital procedures. The systemic vascular resistance was assessed when the participant was in a stable hemodynamic rest state. Reduction from baseline in mean systemic vascular resistance indicates improvement.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

dynes*sec*cm^-5

baseline and week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Pulmonary Vascular Resistance

Change from baseline in pulmonary vascular resistance (dynes*sec*cm^-5) was measured via right heart catheterization according to the local hospital procedures. The pulmonary vascular resistance was assessed when the participant was in a stable hemodynamic rest state. Reduction from baseline in pulmonary vascular resistance indicates improvement.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

dynes*sec*cm^-5

baseline and week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Pulmonary Resistance Index

Change from baseline in pulmonary resistance index (dynes*sec*cm^-5/m2) was measured via right heart catheterization according to the local hospital procedures. The pulmonary resistance index was assessed when the participant was in a stable hemodynamic rest state. A reduction from baseline in pulmonary resistance index indicates improvement.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

dynes*sec*cm^-5/m2

baseline and week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Cardiac Output

Change from baseline in cardiac output (L/min) was measured via right heart catheterization according to the local hospital procedures. The cardiac output was assessed when the participant was in a stable hemodynamic rest state. An increase from baseline (higher number) in cardiac output indicates improvement.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

Liters/minute

24 weeks

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Systolic Arterial Blood Pressure

Change from baseline in systolic arterial blood pressure (mmHg) was measured via right heart catheterization according to the local hospital procedures. The systolic arterial blood was assessed when the participant was in a stable hemodynamic rest state.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

mm Hg

baseline and week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Diastolic Arterial Blood Pressure

Change from baseline in diastolic arterial blood pressure (mmHg) was measured via right heart catheterization according to the local hospital procedures. The diastolic arterial blood pressure was assessed when the participant was in a stable hemodynamic rest state.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

mm Hg

baseline and week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Heart Rate

Change from baseline in heart rate (bpm) was measured via right heart catheterization according to the local hospital procedures. The heart rate was assessed when the participant was in a stable hemodynamic rest state.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

bpm

24 weeks

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Change in Borg Dyspnea Score During 6-minute Walk Test

Change in Borg scale was measured at different time points at week 24. The Borg Scale consists of scale range of 0 to 10. Participants pointed to indicate their level of dyspnea before and at the end of exercise testing (where 0 indicates no breathlessness at all and 10 indicates maximum breathlessness). A reduction in this score indicates an improvement.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Mean

Standard Deviation

units on a scale

week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts
Participants	OG000

Secondary

Covariance of End of Study CAMPHOR Score

The CAMPHOR test consists of 65 items and 3 scales. Two scales measure Health Related Quality of Life. 1) Symptoms: consists of 25 items measuring loss or abnormality of psychological, physiological or anatomical structure or function; further sub-divided into 3 subscales (energy, breathlessness and mood), 2) Disability: consists of 15 items measuring any restriction or lack of ability to perform an activity. 3) Quality of Life (QOL): consists of 25 items defining how individuals perceived ability and capacity to satisfy their needs. The 25-item symptom and QOL scales score from 0-25 where a higher score indicates the presence of more symptoms and poor QOL, respectively. The 15-item functioning scale scores 0-30; a higher score indicates poor functioning.

Participants from the Full Analysis Set, defined as all randomized participants who received at least one dose of study drug, with data available for analysis.

Posted

Least Squares Mean

Standard Error

units on a scale

Week 24

ID	Title	Description
OG000	Imatinib	imatinib mesylate
OG001	Placebo	Placebo to imatinib

Units	Counts

Secondary

Plasma Concentration of QTI571 200 mg and Its Metabolite (GCP74588) Pre-dose and Between 0 Hour to 3 Hour Post-dose Per Participant

Blood samples were taken from each subject participating in the study (placebo group and active treatment group) once predose and once between 0 hour to 3 hour post dose at day 1 (baseline), day 14, day 28 and day 168.

The parent compound QTI571 and its active metabolite, GCP74588, were measured in plasma by validated liquid chromatography-mass spectrometry (HPLC-MS/MS) assay.

The Full Analysis Set includes all patients who received at least one dose of study drug with available blood samples for analysis.

Posted

Mean

Standard Deviation

ng/mL

predose and between 0 hour to 3 hour post dose at day 1, day 14, day 28 and day 168

ID	Title	Description
OG000	Imatinib 200 mg	imatinib mesylate 200 mg once daily
OG001	GCP74588	imatinib metabolite

Units	Counts
Participants	OG000

Secondary

Plasma Concentration of QTI571 400 mg and Its Metabolite (GCP74588) Pre-dose and Between 0 Hour to 3 Hour Post-dose Per Participant

The parent compound QTI571 and its active metabolite, GCP74588, were measured in plasma by validated liquid chromatography-mass spectrometry (HPLC-MS/MS) assay.

The Full Analysis Set includes all patients who received at least one dose of study drug with available blood samples for analysis.

Posted

Mean

Standard Deviation

ng/mL

predose and between 0 hour to 3 hour post dose at day 1, day 14, day 28 and day 168

ID	Title	Description
OG000	Imatinib 400 mg	imatinib mesylate 400 mg once daily
OG001	GCP74588	imatinib metabolite

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0007 affected103 at risk EG0011 affected98 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0010 affected98 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0010 affected98 at risk
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0010 affected98 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0011 affected98 at risk
Atrial flutter	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0011 affected98 at risk
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Nodal arrhythmia	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Right ventricular failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0012 affected98 at risk
Tricuspid valve incompetence	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Periorbital oedema	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Retinal detachment	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected103 at risk EG0012 affected98 at risk
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0011 affected98 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Melaena	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0011 affected98 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Catheter site haemorrhage	General disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Device leakage	General disorders	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Face oedema	General disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Injection site extravasation	General disorders	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Medical device complication	General disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0011 affected98 at risk
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0012 affected98 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0006 affected103 at risk EG0010 affected98 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Hepatic congestion	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Jaundice	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Bacteraemia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Campylobacter infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Clostridial infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Device related infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected103 at risk EG0010 affected98 at risk
Enterocolitis infectious	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0012 affected98 at risk
Gastroenteritis bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Lung infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0012 affected98 at risk
Pneumonia primary atypical	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Pyelonephritis acute	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0010 affected98 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Cardiac output decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
International normalised ratio increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Right atrial pressure increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0011 affected98 at risk
Hypervolaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0010 affected98 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0011 affected98 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Presyncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0005 affected103 at risk EG0010 affected98 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0015 affected98 at risk
Renal failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0011 affected98 at risk
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Renal impairment	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Uterine haemorrhage	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Bronchial haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0006 affected103 at risk EG0012 affected98 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0012 affected98 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0011 affected98 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0011 affected98 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected103 at risk EG0014 affected98 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0014 affected98 at risk
Pulmonary veno-occlusive disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0012 affected98 at risk
Haematoma	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk
Hypertensive crisis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected103 at risk EG0011 affected98 at risk
Hypoperfusion	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0010 affected98 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0008 affected103 at risk EG0012 affected98 at risk
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0004 affected103 at risk EG0017 affected98 at risk
Periorbital oedema	Eye disorders	MedDRA	Systematic Assessment	EG00030 affected103 at risk EG0017 affected98 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected103 at risk EG0013 affected98 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected103 at risk EG0013 affected98 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0016 affected98 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00033 affected103 at risk EG00118 affected98 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0008 affected103 at risk EG0015 affected98 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00056 affected103 at risk EG00123 affected98 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00030 affected103 at risk EG00110 affected98 at risk
Face oedema	General disorders	MedDRA	Systematic Assessment	EG0009 affected103 at risk EG0011 affected98 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG00010 affected103 at risk EG0017 affected98 at risk
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0003 affected103 at risk EG0015 affected98 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG00041 affected103 at risk EG00120 affected98 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0007 affected103 at risk EG0013 affected98 at risk
Device related infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected103 at risk EG0015 affected98 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0015 affected98 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00018 affected103 at risk EG00119 affected98 at risk
Respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected103 at risk EG0017 affected98 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected103 at risk EG0016 affected98 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected103 at risk EG0017 affected98 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected103 at risk EG0015 affected98 at risk
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0009 affected103 at risk EG0011 affected98 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00014 affected103 at risk EG0013 affected98 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00010 affected103 at risk EG0012 affected98 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0005 affected103 at risk EG0016 affected98 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0008 affected103 at risk EG0015 affected98 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00025 affected103 at risk EG00122 affected98 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00011 affected103 at risk EG00115 affected98 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00013 affected103 at risk EG00111 affected98 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0007 affected103 at risk EG0017 affected98 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0006 affected103 at risk EG0014 affected98 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0009 affected103 at risk EG0016 affected98 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0007 affected103 at risk EG0011 affected98 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0003 affected103 at risk EG0015 affected98 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0009 affected103 at risk EG0012 affected98 at risk

ID	Term
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D006973	Hypertension
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Term
D001549	Benzamides
D000577	Amides
D009930	Organic Chemicals
D001565	Benzoates
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011743	Pyrimidines

ID	Title	Description
BG000	Imatinib Mesylate	Imatinib mesylate (QTI571) 200 mg once daily for two weeks, increased to 400 mg once daily if well tolerated. If 400 mg dose was not well tolerated, a down titration to 200 mg once daily was permitted.
BG001	Placebo	Placebo to imatinib mesylate taken once daily. Participants receiving placebo were allowed to receive already approved PAH treatments.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Imatinib	imatinib mesylate			45	103	96	103
EG001	Placebo	Placebo to imatinib			29	98	80	98

ID	Term
D000081029	Pulmonary Arterial Hypertension
D006976	Hypertension, Pulmonary