Imatinib (QTI571) in Pulmonary Arterial Hypertension

NCT ID: NCT00902174

Last Updated: 2016-02-17

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

202 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Study Completion Date

2011-05-31

Brief Summary

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A multinational, multicenter, double blind, placebo-controlled study evaluating the efficacy and safety of imatinib as an add-on therapy in the treatment of patients with severe pulmonary arterial hypertension (PAH).

Detailed Description

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Conditions

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

imatinib mesylate

Intervention Type DRUG

Two or 4 imatinib mesylate (QTI571) 100 mg film coated tablets once daily.

Placebo

Placebo to imatinib mesylate taken once daily. Participants receiving placebo were allowed to receive already approved PAH treatments.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo to imatinib 100 mg film coated tablets

Interventions

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imatinib mesylate

Two or 4 imatinib mesylate (QTI571) 100 mg film coated tablets once daily.

Intervention Type DRUG

Placebo

Placebo to imatinib 100 mg film coated tablets

Intervention Type DRUG

Eligibility Criteria

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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.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Bern, , Switzerland

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Lausanne, , Switzerland

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Sankt Gallen, , Switzerland

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Cambridge, , United Kingdom

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Clydebank, , United Kingdom

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London, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Sheffield, , United Kingdom

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Birmingham, Alabama, United States

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Phoenix, Arizona, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Clearwater, Florida, United States

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Miami Beach, Florida, United States

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Weston, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Minneola, New York, United States

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New York, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Cleveland, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Knoxville, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Milwaukee, Wisconsin, United States

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Innsbruck, , Austria

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Vienna, , Austria

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Brussels, , Belgium

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Leuven, , Belgium

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Calgary, , Canada

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Edmonton, , Canada

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London, , Canada

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Montreal, , Canada

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Ottawa, , Canada

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Toronto, , Canada

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Vancouver, , Canada

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Clamart, , France

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Berlin, , Germany

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Cologne, , Germany

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Dresden, , Germany

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Giessen, , Germany

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Greifswald, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Homburg, , Germany

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Löwenstein, , Germany

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München, , Germany

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Regensberg, , Germany

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Würzberg, , Germany

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Bologna, , Italy

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Pavia, , Italy

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Pisa, , Italy

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Roma, , Italy

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Bunkyō City, , Japan

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Hamamatsu, , Japan

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Mitaka, , Japan

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Okayama, , Japan

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Sendai, , Japan

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Suita, , Japan

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Amsterdam, , Netherlands

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Seoul, , South Korea

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A Coruña, , Spain

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Barcelona, , Spain

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Caceras, , Spain

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Las Palmas de Gran Canarias, , Spain

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Madrid, , Spain

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Málaga, , Spain

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San Cristóbal de La Laguna, , Spain

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Santa Cruz de Tenerife, , Spain

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Santander, , Spain

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Seville, , Spain

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Valencia, , Spain

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Valladolid, , Spain

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Lund, , Sweden

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Stockholm, , Sweden

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Umeå, , Sweden

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Uppsala, , Sweden

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University Hospital Basel

Basel, , Switzerland

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Countries

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United States Austria Belgium Canada France Germany Italy Japan Netherlands South Korea Spain Sweden Switzerland United Kingdom

References

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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.

Reference Type DERIVED
PMID: 26514759 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25367310 (View on PubMed)

Shah AM, Campbell P, Rocha GQ, Peacock A, Barst RJ, Quinn D, Solomon SD; IMPRES Investigators. Effect of imatinib as add-on therapy on echocardiographic measures of right ventricular function in patients with significant pulmonary arterial hypertension. Eur Heart J. 2015 Mar 7;36(10):623-32. doi: 10.1093/eurheartj/ehu035. Epub 2014 Feb 23.

Reference Type DERIVED
PMID: 24566799 (View on PubMed)

Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galie N, Gomez-Sanchez MA, Grimminger F, Grunig E, Hassoun PM, Morrell NW, Peacock AJ, Satoh T, Simonneau G, Tapson VF, Torres F, Lawrence D, Quinn DA, Ghofrani HA. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation. 2013 Mar 12;127(10):1128-38. doi: 10.1161/CIRCULATIONAHA.112.000765. Epub 2013 Feb 12.

Reference Type DERIVED
PMID: 23403476 (View on PubMed)

Related Links

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Other Identifiers

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CQTI571A2301

Identifier Type: -

Identifier Source: org_study_id

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