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

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

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.

Study Overview

• Status: Completed
• Conditions: Myeloproliferative Disorder; Aquagenic Pruritus
• Intervention / Treatment: Drug: Aprepitant 80 mg; Drug: Placebo of Hydroxyzine; Drug: Hydroxyzine 25mg; Drug: Placebo of Aprepitant

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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • CHU d'Angers
  • Caen, France, 14033
    • CHU de Caen
  • Douarnenez, France, 29171
    • Centre Hospitalier de Douarnenez
  • Grenoble, France, 38043
    • Chu Grenoble Alpes
  • Lyon, France, 69373
    • Centre Leon Berard
  • Morlaix, France, 29672
    • Centre Hospitalier Des Pays De Morlaix
  • Nantes, France, 44093
    • CHU de Nantes
  • Rennes, France
    • Hôpital Pontchaillou
  • Saint-Brieuc, France, 22027
    • Hôpital Yves Le Foll
  • Brest Cedex
    • Brest, Brest Cedex, France, 29609
      • CHRU de Brest - Hopital Morvan
  • Quimper
    • Quimper, Quimper, France, 29107
      • Centre Hospitalier de Cornouaille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Investigators: Principal Investigator: Jean-Christophe IANOTTO, MD, PhD, Hématologie Clinique-Institut de Cancéro-Hématologie

Publications and helpful links

General Publications

• Le Gall-Ianotto C, Verdet R, Nowak E, Le Roux L, Gasse A, Fiedler A, Carlhant-Kowalski D, Marcorelles P, Misery L, Ianotto JC. Rationale and design of the multicentric, double-blind, double-placebo, randomized trial APrepitant versus HYdroxyzine in association with cytoreductive treatments for patients with myeloproliferative neoplasia suffering from Persistent Aquagenic Pruritus. Trial acronym: APHYPAP. Trials. 2021 Dec 19;22(1):938. doi: 10.1186/s13063-021-05864-8.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2019
• Primary Completion (Actual): September 1, 2023
• Study Completion (Actual): August 22, 2024

Study Registration Dates

• First Submitted: September 26, 2018
• First Submitted That Met QC Criteria: January 15, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Piperazines; Aprepitant; Hydroxyzine
• Other Study ID Numbers: ApHyPAP 29BRC18.0036; 2018-000426-66 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No