Observational Registry on Patients With Endogenous CS to Document Safety and Effectiveness of Ketoconazole. (KetoPASS)

Prospective, Multi-country, Observational Registry to Collect Clinical Information on Patients With Endogenous Cushing's Syndrome to Assess Drug Utilization Pattern and to Document the Safety and Effectiveness of Ketoconazole.

This is a non-interventional, prospective, multinational, multicentre, observational study, in which data collected are those derived from routine clinical practice via an European registry on CS: ERCUSYN.

Study Overview

• Status: Recruiting
• Conditions: Cushing Syndrome

Detailed Description

The aim is to further document the safety and efficacy of Ketoconazole HRA administered in routine clinical practice in patients with CS.

The study operates under real clinical practice conditions, i.e. there is no treatment protocol thus.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia
    • Recruiting
    • University Hospital Zagreb
    • Contact: susan Webb; Phone Number: +34-93-5565661; Email: swebb@santpau.cat
• France
  • Grenoble, France
    • Recruiting
    • Hôpital Universitaire Grenoble
    • Contact: susan webb, Pr; Phone Number: +34-93-5565661; Email: swebb@santpau.cat
  • Le Kremlin-Bicêtre, France
    • Recruiting
    • Hôpital Bicêtre APHP
    • Contact: susan webb, Pr; Phone Number: +34-93-5565661; Email: swebb@santpau.cat
  • Marseille, France
    • Recruiting
    • Hopital de la conception
    • Contact: susan webb, Pr; Phone Number: +34-93-5565661; Email: swebb@santpau.cat
• Spain
  • Barcelona, Spain
    • Recruiting
    • Institut de Recerca de la Santa Creu i Sant Pau
    • Contact: susan webb, Pr; Phone Number: +34-93-5565661; Email: swebb@santpau.cat
• Sweden
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital
    • Contact: susan webb, Pr; Phone Number: +34-93-5565661; Email: swebb@santpau.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will include all patients aged 12 years and above with endogenous CS from all causes exposed to ketoconazole and included by the participating centers in ERCUSYN. Patients with CS due to an adrenal carcinoma will be excluded from the study population since adrenal carcinoma is excluded from ERCUSYN registry.

Description

Inclusion Criteria:

1. Male or female patients aged from 12 years or older with a diagnosis of CS
2. Patients who started ketoconazole therapy after study start
3. For patients previously treated with ketoconazole, patients must have taken their last dose at least 6 months before starting ketoconazole again in this study.
4. Written informed consent signed prior to registration of any patient data in HRA modules.

Exclusion Criteria:

1. Adrenal cortical carcinoma
2. Patients currently participating in any other trial (interventional or not) of an investigational medicine or participation in the past one month before start of ketoconazole
3. Patients who have at least one contraindication among those listed in section 4.3 of the ketoconazole SmPC

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of hepatotoxicity and QT prolongation to assess liver and cardiac tolerability profile of ketoconazole.	The primary objective is to document liver and cardiac tolerability profile of ketoconazole p.o when administered as monotherapy or in combination with other therapies, in routine clinical practice, in patients with CS.	up to 5 years of follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events	Number of adverse events with Ketoconazole in monotherapy or in combination with other therapies for Cushing Syndrome.	up to 5 years of follow up
Drug utilization pattern regarding safe utilization of ketoconazole according to HRA SmPC recommendations on liver function	Number of liver tests performed per patient Number of patients for whom LFTs were performed according to SmPC recommendations. Number of patients with reduction of ketoconazole dose following liver enzymes increase Number of patients with interruptions / definitive stop of ketoconazole following liver enzymes increase	up to 5 years of follow up
Drug utilization pattern of ketoconazole according to HRA SmPC recommendations on liver function	Timing of liver tests performed per patient according to defined windows.	up to 5 years of follow up
Drug utilization pattern regarding safe use of ketoconazole according to HRA SmPC recommendations on liver function	Percentage of patients for whom LFTs were performed according to SmPC recommendations. Percentage of patients with reduction of ketoconazole dose following liver enzymes increase Percentage of patients with interruptions / definitive stop of ketoconazole following liver enzymes increase	up to 5 years of follow up
Drug utilization pattern regarding safe utilization of ketoconazole according to HRA SmPC recommendations on Qt interval monitoring.	Number of ECGs performed per patient Number of patients for whom ECGs were performed according to SmPC recommendations	up to 5 years of follow up
Drug utilization pattern of ketoconazole according to HRA SmPC recommendations on Qt interval monitoring.	Timing of ECGs performed per patient according to defined windows	up to 5 years of follow up
Drug utilization pattern regarding safe use of ketoconazole according to HRA SmPC recommendations on Qt interval monitoring.	Percentage of patients for whom ECGs were performed according to SmPC recommendations	up to 5 years of follow up
Effectiveness of ketoconazole	clinical outcome evaluated by the physician after ketoconazole treatment: cortisol levels improvement or normalization after ketoconazole treatment clinical symptoms of Cushing Syndrome over time. Number and type of comorbidities. Number of concomitant treatments for comorbidities by drug class.	up to 5 years of follow up
Impact on Quality of life, European Quality of Life questionnaire	self-administered questionnaire of Health-Related Quality of Life to evaluate current health regarding mobility, self-care, usual activities, pain/discomfort and anxiety/depression, and the perceived health status of the patient. The answers given can be converted into utility scores anchored at 0 for death and 1 for perfect health. The questionnaire also includes a Vi-sual Analog Scale (VAS), by which respondents can reporttheir perceived health status with a grade ranging from 0(the worst possible health status) to 100 (the best possiblehealth status).	up to 5 years of follow up
Impact on Quality of life, Cushing Quality of Life questionnaire	items referring to problems relevant to patients with CS with five categories of response. Answers are rated on a scale of 1-5, where '1' corresponds to 'Always' or 'Very much' and '5' to 'Never' or 'Not at all'. Therefore, the lower the score, the greater the impact on Health-Related Quality of Life.	up to 5 years of follow up

Collaborators and Investigators

• Sponsor: HRA Pharma

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2018
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: February 16, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 30, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Syndrome; Cushing Syndrome
• Other Study ID Numbers: Keto PASS

Drug and device information, study documents

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