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The Efficacy and Safety of Vardenafil in the Treatment of Pulmonary Arterial Hypertension (EVALUATION)

This study has been completed.
Sponsor:
Information provided by:
Tongji University
ClinicalTrials.gov Identifier:
NCT00718952
First received: July 18, 2008
Last updated: February 11, 2010
Last verified: February 2010
  Purpose

The purpose of this study is to evaluate the efficacy and safety of vardenafil in the treatment of pulmonary arterial hypertension.


Condition Intervention Phase
Pulmonary Hypertension
Drug: Vardenafil
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Multi-centre, Prospective, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Treatment of Pulmonary Arterial Hypertension With Vardenafil in China

Resource links provided by NLM:


Further study details as provided by Tongji University:

Primary Outcome Measures:
  • The change in exercise capacity, as measured by the total distance walked in six minutes [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The reduction of mean pulmonary-artery pressure(mPAP)and pulmonary vascular resistance(PVR) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  • The increase of cardiac output(CO) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  • The increase of Peripheral Saturation of oxygen(SPO2) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  • The change in the Borg dyspnea index(a measure of perceived breathlessness on a scale of 0 to 10, with higher values indicating more severe dyspnea) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  • The change in World Health Organization (WHO) functional classification of pulmonary arterial hypertension (an adaptation of the New York Heart Association classification) [ Time Frame: at week 12 and week 24 ] [ Designated as safety issue: No ]
  • Time from randomization to clinical worsening(defined as death, transplantation,hospitalization for PAH and worse right heart failure,acute heart failure,or vardenafil allergy,or worsening leading to discontinuation,need for epoprostenol or bosentan) [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: July 2008
Study Completion Date: February 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Patients in group A will receive vardenafil in double-blinded treatment period.
Drug: Vardenafil
vardenafil tablet 5mg once-daily orally in the first 4 weeks while 5mg twice-daily orally in the following 8 weeks.
Other Name: Levitra
Drug: Vardenafil
Patients in all the 2 arms will take vardenafil tablet 5mg twice-daily orally from week 13 to week 24(open-label).
Other Name: Levitra
Placebo Comparator: B
Patients in group A will receive placebo in double-blinded treatment period.
Drug: Placebo
Placebo tablet 5mg once-daily orally in the first 4 weeks while 5mg twice-daily orally in the following 8 weeks.
Drug: Vardenafil
Patients in all the 2 arms will take vardenafil tablet 5mg twice-daily orally from week 13 to week 24(open-label).
Other Name: Levitra

Detailed Description:

Pulmonary arterial hypertension (PAH), defined as a mean pulmonary artery pressure ≥25 mmHg with a pulmonary capillary wedge pressure ≤15 mmHg measured by cardiac catheterization, is a disorder that may occur either in the setting of a variety of underlying medical conditions or as a disease that uniquely affects the pulmonary circulation. Irrespective of its etiologies, PAH is a serious and often progressive disorder that results in right ventricular dysfunction and impairment in activity tolerance, and may lead to right-heart failure and death. The pathogenesis of PAH is complex and incompletely understood, but includes both genetic and environmental factors that alter vascular structure and function.

In recent years, several new drugs have been developed for the treatment of pulmonary arterial hypertension (PAH), including continuous intravenous epoprostenol, inhaled iloprost, subcutaneous trepostinil, oral bosentan, and oral beraprost. In addition, there is increasing evidence for the therapeutic effectiveness of the phosphodiesterase-5 (PDE-5) inhibitor sildenafil in PAH. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide (NO) .The phosphodiesterases have different tissue distributions and substrate affinities. Interestingly, PDE-5 is abundantly expressed in lung tissue, thus offering as target molecule for PAH treatment concepts.

The three commercially available PDE-5 inhibitors (sildenafil, vardenafil, and tadalafil) are currently approved for the treatment of erectile dysfunction . These inhibitors are now receiving attention for their activity in the pulmonary vasculature. Sildenafil has been proved to improve the exercise capacity and pulmonary hemodynamics of PAH patients, however, there are few reports regarding the use of vardenafil or tadalafil on the pulmonary vasculature. Although sildenafil, vardenafil, and tadalafil act on the same enzyme, these drugs exhibit different pharmacokinetics and selectivity, and therefore may not be equally efficacious in the pulmonary vascular bed. As vardenafil has a more than 20-fold greater potency than sildenafil for inhibiting purified PDE-5, we assume that it will show more favorable clinical and side-effect profiles in treating PAH.

This is a prospective, randomized, placebo-controlled, pilot study to evaluate the efficacy and safety of vardenafil in the treatment of pulmonary arterial hypertension.

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects aged 12-65.
  • Confirmed idiopathic pulmonary hypertension, connective tissue disease associated pulmonary hypertension, congenital heart disease(with Eisenmenger syndrome) associated pulmonary hypertension.
  • Baseline 6-minutes walking distance 150m-550m.
  • WHO pulmonary hypertension function II-III with non-responder to calcium channel blockers.
  • Documented written informed consent.

Exclusion Criteria:

  • The other types of pulmonary hypertension.
  • Subjects who refuse to subscribe written informed consents or can't cooperate with the trial well.
  • Subjects with serious acute or chronic disease involved liver, kidney, and brain or have to use potent CYP3A4-inhibitor or nitrate to treat the underlying diseases.
  • Subjects who are currently treated with sildenafil for PAH or taking sildenafil or tadalafil.
  • Other contraindications in package insert.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00718952

Locations
China, Beijing
Peking University First Hospital
Beijing, Beijing, China, 100034
Peking Union Hospital, Peking Union Medical College
Beijing, Beijing, China, 100730
Peking University First Hospital
Beijing, Beijing, China, 100043
Beijing Shijitan Hospital, Peking University
Beijing, Beijing, China
China, Heilongjiang
The First Clinical College of Harbin Medical University
Harbin, Heilongjiang, China
China, Hunan
Xiangya Hospital, Central-South University
Changsha, Hunan, China, 410008
China, Liaoning
The General Hospital of Shenyang Military Command
Shenyang, Liaoning, China
China, Shanghai
Renji Hospital, Shanghai Jiaotong University
Shanghai, Shanghai, China, 200127
China, Shanxi
The First Affiliated Hospital of Medical College of Xian Jiaotong University
Xi'an, Shanxi, China, 710061
China
Shanghai Pulmonary Hospital ,Tongji University
Shanghai, China, 200433
Sponsors and Collaborators
Tongji University
Investigators
Principal Investigator: Zhi-Cheng Jing, MD Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai, China
  More Information

Publications:

Responsible Party: Professor Zhi-Cheng JING, Shanghai Pulmonary Hospital, Tongji University,Shanghai, China
ClinicalTrials.gov Identifier: NCT00718952     History of Changes
Other Study ID Numbers: EVALUATION-01
Study First Received: July 18, 2008
Last Updated: February 11, 2010
Health Authority: China: Food and Drug Administration

Keywords provided by Tongji University:
Pulmonary Hypertension

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Vardenafil
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on November 20, 2014