REDucing Hot FLASHes in Women Using Endocrine Therapy. (REDFLASH)

A Randomized Intrapatient Cross-over Study to Assess the Efficacy of Oxybutynin Versus Venlafaxine in Reducing Hot Flashes in Women Using Endocrine Therapy After Breast Cancer.

The goal of this randomized intrapatient cross-over study is to assess the efficacy of oxybutynin versus venlafaxine in reducing hot flashes in women using endocrine therapy after breast cancer.

The objectives it aims to answer are:

• To assess the efficacy of oxybutynin versus venlafaxine in reducing hot flashes in women using endocrine therapy after breast cancer
• To assess side effects of oxybutynin versus venlafaxine.
• To assess the personal preference of women for oxybutynin versus venlafaxine in reducing hot flashes.
• To assess quality of life of women when reducing hot flashes in women using endocrine therapy after breast cancer.

Participants will fill-out a patient diary during 15 weeks total on a daily basis and receive an (online) questionnaire three times total.

Researchers will compare two groups (venlafaxine group versus oxubutynine group) to assess its efficacy concerning hot flashes.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Hot Flash Due to Medication
• Intervention / Treatment: Drug: Oxybutynin; Drug: Venlafaxine

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marte Smits, MSc; Phone Number: +31152603870; Email: marte.smits@rdgg.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Delft, Zuid-Holland, Netherlands, 2625 AD
      • Recruiting
      • Reinier de Graaf Gasthuis
      • Contact: Maaike de Leeuw, MSc; Phone Number: +31152603035; Email: M.deLeeuw@rdgg.nl
      • Contact: Marte Smits, MSc
      • Contact: Lemonitsa Mammatas, PHD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pre-, peri- or postmenopausal women of 18 years or above;
• Indication for endocrine therapy and already started with tamoxifen, aromatase inhibitors or luteinizing hormone-releasing hormone analogues for at least 4 weeks and planning to continue for the duration of the study;
• Experiencing hot flashes with a minimum of 14 per week for at least 1 month and desire to start a pharmacologic intervention.

Exclusion Criteria:

• Pregnant;
• Breast feeding;
• Patients who receive chemotherapy or immunotherapy/HER2 antibodies within the prior 8 weeks, and patients scheduled for chemotherapy during the study period;
• Palliative setting;
• Use of venlafaxine or any other antidepressants, also including St. John's wort within the previous year;
• Creatinine clearance < 30 ml/min;
• Liver cirrhosis;
• Use of gabapentin and/or calcium channel antagonists within 2 weeks of study entry;
• Use of oxybutynin before study entry;
• Use of any other substances or therapies for the treatment of hot flashes, for instance acupuncture.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venlafaxine; In this open-label randomized controlled intrapatient cross-over study patients are randomly assigned to one of the two treatment groups. After a one week baseline period, group 1 starts with venlafaxine 37.5 mg once daily for 7 days followed by 75 mg once daily for 5 weeks followed by a two-week wash-out period (no medication), hereafter the group starts with oxybutynin 5 mg twice per day for 6 weeks total.	Drug: Oxybutynin; Oxybutynin 5 mg twice per day for 6 weeks; Drug: Venlafaxine; Venlafaxine 37.5 mg once daily for 7 days followed by 75 mg once daily for 5 weeks
Experimental: Oxybutynin; After a one week baseline period, group 2 starts with oxybutynin 5 mg twice per day for 6 weeks total followed by a two-week wash-out period (no medication), hereafter the group starts with venlafaxine 37.5 mg once daily for 7 days followed by 75mg once daily for 5 weeks.	Drug: Oxybutynin; Oxybutynin 5 mg twice per day for 6 weeks; Drug: Venlafaxine; Venlafaxine 37.5 mg once daily for 7 days followed by 75 mg once daily for 5 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and severity of hot flashes	Number and severity of hot flashes during 6-weeks of therapy measured by the Hot Flash Diary.	15 weeks total

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life and health status	Quality of life and health status at baseline and after 6 weeks of treatment measured by the EORTC-QLQ-C30	15 weeks total
Adverse effects of treatments	Adverse effects of treatments weekly measured by the National Cancer Institute Common Toxicity Criteria scale, version 5	15 weeks total
Sleep quality	Sleep quality at baseline and after 6 weeks of treatment measured by the Groningen Sleep Quality Scale (GSQ)	15 weeks total
Anxiety and depression	Anxiety and depression measured at baseline and after 6 weeks of treatment with the Hospital Anxiety and Depression Scale (HADS)	15 weeks total
Sexual function	Sexual function measured at baseline and after 6 weeks of treatment with the Sexual Activity Questionnaire (SAQ)	15 weeks total
Cognitive function	Cognitive function measured at baseline and after 6 weeks of treatment with the 6-item cognitive impairment test (6-CIT)	15 weeks total
Adherence	Ask patients the following question after 6 weeks of treatment: 'Would you like to continue the endocrine therapy for the recommended duration of therapy taking the current medication (oxybutynin or venlafaxine) given the number and severity of hot flashes you experience during the last week?'	15 weeks total
Preference	Ask patients the following question after 6 weeks of the final treatment: 'Do you have a preference taking the medication from study period 1 or study period 2?'	15 weeks total

Collaborators and Investigators

• Sponsor: Reinier de Graaf Groep
• Investigators: Principal Investigator: Lemonitsa Mammatas, PhD, Reinier de Graaf Ziekenhuis

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: October 24, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Hot Flashes; Serotonin and Noradrenaline Reuptake Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Antidepressive Agents; Urological Agents; Antidepressive Agents, Second-Generation; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Parasympatholytics; Venlafaxine Hydrochloride; Oxybutynin
• Other Study ID Numbers: REDFLASH2023-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study protocol, anonymised database and study results may be available on request, after assessment of the reason for request by the study investigators.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No