Aprepitant Versus Hydroxyzine in Persistent Aquagenic Pruritus for Patients With Myeloproliferative Neoplasms

Study Overview
=================
Brief Summary
-----------------
Phase 3, randomized prospective study, double blind-double placebo, testing oral therapies APREPITANT versus HYDROXYZINE in patients followed for myeloproliferative neoplasms and suffering of persistent aquagenic pruritus.

Detailed Description
-----------------
Identification of patients with myeloproliferative neoplasms and aquagenic pruritus. Evaluation of the intensity of the aquagenic pruritus. Patients with value >5/10 on the VAS (Visual Analogue Scale ) are proposed to participate to the protocole. Randomization between the two treatments. Duration of the treatment : 14 days. Regular evaluation of efficacity of the drugs (questionnaires). Evaluations will stop 2 months after the last intake. Blood samples will be collected before and after the intakes to study cytokine and neuropeptide levels.

Official Title
-----------------
Aprepitant Versus Hydroxyzine in Association With Cytoreductive Treatments for Patients With Myeloproliferative Neoplasia Suffering From Persistent Aquagenic Pruritus.

Conditions
-----------------
Myeloproliferative Disorder, Aquagenic Pruritus

Intervention / Treatment
-----------------
* Drug: Aprepitant 80 mg
* Drug: Hydroxyzine 25mg
* Drug: Placebo of Hydroxyzine
* Drug: Placebo of Aprepitant


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Major patients with myeloproliferative neoplasms (polycythemia vera, essential thrombocythaemia or myelofibrosis) and treated with hydroxyurea, pipobroman, anagrelide, α2a pegylated interferon, ruxolitinib or bled for more than 6 months and suffering of persistent aquagenic pruritus and with a pruritus intensity on Analogic Visual Scale >5/10 patients who gave their written consent for participation in the study Exclusion Criteria: patients with a physical or psychological disability to sign the consent form patients with myeloproliferative neoplasms and suffering of aquagenic pruritus but only treated by aspirin patients already included in another therapeutic protocol patients with diffuse dermatological disease where pruritus may be present (psoriasis, atopic dermatitis, prurigo patients already on anti-anxiety and / or anti-depressant treatment patients with absolute contraindications to the use of Aprepitant or Hydroxyzine hypersensitivity to Aprepitant and / or Hydroxyzine or to any of their excipients lactose intolerance pregnant or lactating women

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 3, randomized prospective study, double blind-double placebo
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: studied group<br>Aprepitant 80 mg daily - 14 days Plus placebo of Hydroxyzine - 14 days | Drug: Aprepitant 80 mg<br>* oral therapy - daily dose - 14 days<br>Drug: Placebo of Hydroxyzine<br>* oral therapy - daily dose - 14 days<br>|
| Active Comparator: comparative group<br>Hydroxyzine 25 mg/d - 14 days Plus placebo of Aprepitant - 14 days | Drug: Hydroxyzine 25mg<br>* oral therapy - daily dose - 14 days<br>Drug: Placebo of Aprepitant<br>* oral therapy - daily dose - 14 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of pruritus intensity below (or equal) 3/10 on the VAS (Visual Analogue Scale ) | number of patients with a pruritus intensity below (or equal) 3/10 on the VAS (Visual Analogue Scale wich measure the intensity of symptoms of pruritus, 0 is minimum and 10 is maximum intensity of symptoms) | at 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of pruritus intensity below (or equal) 3/10 on the VAS (Visual Analogue Scale ) | number of patients with a pruritus intensity below (or equal) 3/10 on the VAS (Visual Analogue Scale wich measure the intensity of symptoms of pruritus, 0 is minimum and 10 is maximum intensity of symptoms) | at 60 days | 
| Cessation of pruritus | number of patients with a pruritus intensity at 0/10 on the VAS (Visual Analogue Scale wich measure the intensity of symptoms of pruritus, 0 is minimum and 10 is maximum intensity of symptoms) ) | at 15 days | 
| Cessation of pruritus | number of patients with a pruritus intensity at 0/10 on the VAS (Visual Analogue Scale wich measure the intensity of symptoms of pruritus, 0 is minimum and 10 is maximum intensity of symptoms)) | at 60 days | 
| Time observed to decreased the VAS to 3/10 | number of days to obtain an intensity of pruritus at 3/10 on the VAS (Visual Analogue Scale ) | 01 to 60 days | 
| Duration of treatment effectiveness | number of days the VAS (Visual Analogue Scale ) is below (or equal) 3/10 | 1 to 60 days | 
| Adverse event occurring during the association therapeutic | type of adverse event occuring during the treatment period | at 15 days | 
| Number of prematurely discontinued anti-pruritic treatment | Total number of prematurely discontinued treatments for all subjects | at 15 days | 
| Complete blood count (normal or abnormal) | number of patients with hematologic remission : hematocrit <45% with leukocytes <10 giga/l and platelets <400 giga/l | 1 to 60 days | 
| Quality of life through the use of validated questionnaire : the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) questionnaire | Evaluation of quality of life by completion of the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form calculated as the mean score for 10 items. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers) questionnaire | at J0 (day of inclusion) | 
| Quality of life through the use of validated questionnaire : the PASYMPLE questionnaire | Evaluation of quality of life by completion of the PASYMPLE (evaluation of pruritus with 7 questions about occurence, timing, intensity and localisation of pruritus) questionnaire | at J0 (day of inclusion) | 
| Quality of life through the use of validated questionnaire : the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) questionnaire | Evaluation of quality of life by completion of the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form calculated as the mean score for 10 items. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers)questionnaire | at 15 days | 
| Quality of life through the use of validated questionnaire : the PASYMPLE questionnaire | Evaluation of quality of life by completion of the PASYMPLE (evaluation of pruritus with 7 questions about occurence, timing, intensity and localisation of pruritus) questionnaire | at 15 days | 
| Quality of life through the use of validated questionnaires : the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) questionnaire | Evaluation of quality of life by completion of the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form calculated as the mean score for 10 items. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers) questionnaire | at 30 days | 
| Quality of life through the use of validated questionnaire : the PASYMPLE questionnaire | Evaluation of quality of life by completion of the PASYMPLE (evaluation of pruritus with 7 questions about occurence, timing, intensity and localisation of pruritus) questionnaire | at 30 days | 
| Quality of life through the use of validated questionnaire : the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) questionnaire | Evaluation of quality of life by completion of the MPN-SAF(Myeloproliferative Neoplasm Symptom Assessment Form calculated as the mean score for 10 items. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers) questionnaire | at 45 days | 
| Quality of life through the use of validated questionnaire : the PASYMPLE questionnaire | Evaluation of quality of life by completion of the PASYMPLE (evaluation of pruritus with 7 questions about occurence, timing, intensity and localisation of pruritus) questionnaire | at 45 days | 
| Quality of life through the use of validated questionnaire : the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) questionnaire | Evaluation of quality of life by completion of the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form calculated as the mean score for 10 items. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers) questionnaire | at 60 days | 
| Quality of life through the use of validated questionnaire : the PASYMPLE questionnaire | Evaluation of quality of life by completion of the PASYMPLE (evaluation of pruritus with 7 questions about occurence, timing, intensity and localisation of pruritus) questionnaire | at 60 days | 
| Quantification of the change of plasma concentrations of cytokines and neuropeptides | Plasma concentrations of cytokines (ng/L) and neuropeptides (ng/mL) | at J0 (day of inclusion) | 
| Quantification of the change of plasma concentrations of cytokines and neuropeptides | Plasma concentrations of cytokines (ng/L) and neuropeptides (ng/mL) | at 15 days | 
| Quantification of the change of plasma concentrations of cytokines and neuropeptides | Plasma concentrations of cytokines (ng/L) and neuropeptides (ng/mL) | at 30 days | 
| Quantification of the change of plasma concentrations of cytokines and neuropeptides | Plasma concentrations of cytokines (ng/L) and neuropeptides (ng/mL) | at 60 days |