Qutenza®-Remodulin® in Pulmonary Arterial Hypertension Patients

Study Overview
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Brief Summary
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The investigators hypothesise that pre-application of Qutenza® patches to the skin may reduce pain at the site of Remodulin® SC infusion (sited 1 to 2 weeks later at the site of Qutenza pre-application), in which case it would greatly improve the quality of life of the patients, and enable many more to continue with this treatment. It may also provide new information to support the use of Qutenza® patches for preventing and reducing pain produced by inflammation. The present study will explore the efficacy of single applications of Qutenza® (capsaicin 8% patch) in reducing site pain caused by continuous SC infusion of Remodulin®, in pulmonary arterial hypertension patients, as assessed by changes in subjective pain rating score and/or pain and sensory testing.

Official Title
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A Double-blind, Randomized, Crossover Clinical Study to Assess the Efficacy of Qutenza® for the Reduction of Site Pain Caused by Continuous Subcutaneous Infusion of Remodulin®, in Pulmonary Arterial Hypertension Patients

Conditions
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Pulmonary Hypertension, Pain

Intervention / Treatment
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* Drug: Qutenza
* Drug: Tegaderm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older with symptomatic PAH Willing to provide written informed consent to participate in the study. With documented diagnosis of PAH, either idiopathic, familial or associated with connective tissue disease, congenital heart disease or the use of anorexogenic drugs. Documented haemodynamic diagnosis of PAH by right heart catheterization - performed at any time prior to screening, showing: mean pulmonary arterial pressure >25 mm Hg, pulmonary capillary wedge pressure =/< 15 mmHg and pulmonary vascular resistance >240 dynes/sec/cm Receiving stable doses of Remodulin® SC, continuously infused at a dose of at least 2.5 ng/kg/min for at least 8 weeks prior to enrolment. Additional medications that are approved for treatment of PAH (either bosentan or sildenafil) and other supplementary treatments such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. History of pain at the site of Remodulin® SC infusion for at least 8 weeks prior to enrolment and as assessed on the 11 point pain intensity numerical pain rating scale (NPRS) from 0 to 10, where 0 represents No pain and 10 represents Maximum pain imaginable. Patients with a history of pain intensity equal or greater than 3 NPRS points (as determined by the NPRS trial diary completed during the screening period) are eligible to participate. Modified New York Heart Association (NYHA) (WHO) classification II-IV that has been stable for at least 8 weeks prior to enrolment. A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol <40 pg/ml (<140 pmol/L) is confirmatory]. Child-bearing potential and agrees to use one of the contraception methods listed in the protocol. Exclusion Criteria: Patient's participating in another clinical trial or who have done so within 30 days before screening. Patients with PAH in NYHA/WHO functional class I at screening. Known to be positive for human immunodeficiency virus (HIV). Patients with any additional medical condition or illness that, in the opinion of the Investigator would interfere with study compliance and/or impair the patient's ability to participate or complete the study. Patients with a history of substance abuse (e.g. alcohol or drug abuse) within the previous 6 months before enrolment. Patients with a history of severe allergies or multiple drug allergies and/or reported hypersensitivity to capsaicin. Patients with no history of pain at the site of Remodulin® SC infusion or average pain intensity at screening less than 3 points on the numerical pain rating scale (NPRS). Life expectancy less than 12 months. Unable to provide informed consent. Female patients who are lactating or pregnant (positive pre-randomisation serum pregnancy test) or plan to become pregnant during the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Tegaderm<br> | Drug: Tegaderm<br>* No active drug<br>|
| Active Comparator: Qutenza<br> | Drug: Qutenza<br>* 8% patch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Measures | Safety evaluations will be based on the incidence, intensity and type of AEs and clinically significant changes in vital signs (pulse rate, blood pressure, respiration rate, pulse oximetry and temperature), and changes in concomitant medications throughout the study. Evaluation of safety will also be based on subject's physical examination, signs and symptoms of PAH, routine clinical laboratory tests (hematology, chemistry, coagulation panel, and urinalysis), ECG, and NYHA (WHO) classification at the screening and end of study follow up visits. | Approximately 9 months (vital signs, AE's and concomitant medications will be recorded throughout the study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy measure - change in mean NPRS score | The primary efficacy measure will be the change in mean NPRS pain score (reduced by greater than 1.1) at the site of Remodulin® SC infusion, following Qutenza® or transparent adhesive control dressing (Tegaderm film 10cmx12cm) in combination with 0.075% capsaicin cream (Axsain®), during two treatment periods. Efficacy of Qutenza® relative to the control will also be assessed on PGIC, as well as sensory tests and flare area. | Approximately 9 months. Average daily NPRS scores from Weeks 1 and 2 of each treatment period will be expressed as percentage changes from the average daily NPRS score at baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Hypertension, Pain