Impact of Transferrin Saturation Guided Maintenance Treatment on Quality of Life in HFE Haemochromatosis

Not Applicable

Recruiting

• Conditions: Haemochromatosis
• Interventions: Other: Clinical examination; Other: SF36 questionnaire; Other: AIMS2_SF questionnaire; Other: WOMAC questionnaire; Other: EQ-5D-5L questionnaire; Biological: Blood Sample Complete blood count; Biological: Blood Sample Iron panel; Biological: Blood Sample Fasting Glucose; Biological: Blood sample lipid panel; Biological: Blood sample liver panel; Biological: Blood sample C reactive protein; Biological: BioBank; Procedure: Bloodletting - control group; Other: Medico-economical; Procedure: Bloodletting - experimental group

• Registration Number: NCT04779593
• Lead Sponsor: Rennes University Hospital

Brief Summary

Patients in maintenance treatment for HFE hemochromatosis since at least one year will be included in a two year study period and randomized in two groups experimental and control group. Because proton pump inhibitors are widely used as chronic medication, and because they can significantly modify iron absorption, patients will be stratified according to the use of proton pump inhibitors and gender. A first bloodletting will be performed at inclusion with the same volume as usually performed by the patients. Results of the biological test performed at this visit will guide the time schedule and volume of the next bloodletting according to randomization group (patients treated with bloodletting according to current guidelines "ferritin alone" versus patients treated with bloodletting according to "transferrin saturation and serum ferritin").Blood count and iron metabolism parameters will be performed at each bloodletting and follow-up visits. Time schedule and volume of bloodletting will be adjusted to biological results after each follow-up visit. Volume and schedule for bloodlettings will be determined according to guidelines specifically designed for this study to assure harmonization of treatment management, and centrally validated through the recording of the biological tests in the electronic Case Report Form which will provide the investigator with the volume and schedule of the next bloodletting. There will be two ways of treatment modification: either change of schedule or volume of bloodletting. Patients will undergo follow-up visit every six months with clinical examination, questionnaires at J0, M12 and M24 (SF-36; AIMS2-SF, WOMAC, EQ-5D-5L), and biological test. For health economics analysis, data will be obtained thanks to a dedicated extraction from SNDS database SNDS database will allow to gather hospital stays, visits, and other healthcare-related costs as well as vital status (date (month/year) of death) and cause of death. A de-identified copy of the clinical database, restricted to the relevant variables, will be sent for semideterministic matching purpose with SNDS extraction using four key variables: gender, same date (month/year) of birth, same date (day/month/year) of visit for bloodletting; pending, of course, regulatory authorization.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-02
• Study First Submitted QC: 2021-03-02
• Study First Posted: 2021-03-03
• Study Start: 2021-07-02
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-16
• Last Update Posted: 2023-01-18
• Primary Completion: 2027-01
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• • Patients treated with iron chelators;
• Patients treated with erythroid growth factors (erythropoietin);
• Patient with excessive alcohol consumption (> 20g/day and > 30 g/day for women and men respectively);
• Patients with chronic haematological condition;
• Patients having uncontrolled chronic blood loss (of digestive or gynaecological origin);
• Patients with chronic kidney failure;
• Patients with a diagnosis of cancer or history of cancer in the last year;
• Pregnancy or breast feeding.
• Patient who are included in another research protocol
• Adults legally protected (judicial protection, guardianship, or supervision), persons deprived of their freedom.
• with C282Y homozygous HFE hemochromatosis;
• having finished the initial phase of HFE hemochromatosis treatment and in maintenance treatment for at least one year;
• having signed an informed consent form.

Exclusion Criteria

• Patients treated with iron chelators;
• Patients treated with erythroid growth factors (erythropoietin);
• Patient with excessive alcohol consumption (> 20g/day and > 30 g/day for women and men respectively);
• Patients with chronic haematological condition;
• Patients having uncontrolled chronic blood loss (of digestive or gynaecological origin);
• Patients with chronic kidney failure;
• Patients with a diagnosis of cancer or history of cancer in the last year;
• Pregnancy or breast feeding.
• Patient who are included in another research protocol
• Adults legally protected (judicial protection, guardianship, or supervision), persons deprived of their freedom.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
experimental group	SF36 questionnaire	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	Blood Sample Iron panel	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	Blood Sample Complete blood count	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	Blood sample C reactive protein	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	Blood sample liver panel	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	BioBank	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	Clinical examination	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	Blood sample lipid panel	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
control group	Blood Sample Complete blood count	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	Bloodletting - control group	Patients treated with bloodletting according to current guidelines "ferritin alone"
experimental group	AIMS2_SF questionnaire	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	WOMAC questionnaire	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	EQ-5D-5L questionnaire	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	Blood Sample Fasting Glucose	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
experimental group	Medico-economical	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
control group	Clinical examination	Patients treated with bloodletting according to current guidelines "ferritin alone"
experimental group	Bloodletting - experimental group	Patients treated with bloodletting according to "transferrin saturation and serum ferritin".
control group	WOMAC questionnaire	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	SF36 questionnaire	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	AIMS2_SF questionnaire	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	EQ-5D-5L questionnaire	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	Blood Sample Fasting Glucose	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	Blood sample liver panel	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	BioBank	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	Blood Sample Iron panel	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	Blood sample lipid panel	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	Blood sample C reactive protein	Patients treated with bloodletting according to current guidelines "ferritin alone"
control group	Medico-economical	Patients treated with bloodletting according to current guidelines "ferritin alone"

Primary Outcome Measures

Name	Time	Method
The primary evaluation criteria is the Physical Component Score of the SF-36 questionnaire at the end of the study period (two years)	At Month 24	The primary evaluation criteria is the Physical Component Score of the SF-36 questionnaire at the end of the study period (two years). Physical Component score of the SF-36 has been chosen because SF-36 it is a widely validated and reproducible questionnaire, and this component is best susceptible to reflect both fatigue and joint involvement.

Secondary Outcome Measures

Name	Time	Method
Evolution of the Physical Component Score of the SF-36	at Day 0, Month 12 and Month 24 follow-up visit	Evolution of the Physical Component Score of the SF-36 throughout the study, as performed at J0, M12 and M24 follow-up visit (every 12 months).
the AIMS2- SF (short form of the Arthritis Impact Measurement Scales 2) questionnaire	at Day 0, Month 12 and Month 24 follow-up visit	Assessment of Arthropathy and joint pain related quality of life as assessed by the AIMS2- SF (short form of the Arthritis Impact Measurement Scales 2) questionnaire throughout the study, as performed at J0, M12 and M24 follow-up visit (every 12 months).
Total number of phlebotomy performed	At Month 24	Total number of phlebotomy performed by each patient during the study period.
the WOMAC (Western Ontario and McMaster Universities Arthritis Index) questionnaire	at Day 0, Month 12 and Month 24 follow-up visit	Assessment of Arthropathy and joint pain related quality of life as assessed by the WOMAC (Western Ontario and McMaster Universities Arthritis Index) questionnaire throughout the study, as performed at J0, M12 and M24 follow-up visit (every 12 months).
Evolution of the Mental Component Score of the SF-36	at Day 0, Month 12 and Month 24 follow-up visit	Evolution of the Mental Component Score of the SF-36 throughout the study, as performed at J0, M12 and M24 follow-up visit (every 12 months).
Occurrence of malaise	At Month 24	Occurrence of malaise after a bloodletting procedure
Evolution of the Mental Component Score of the SF-36 questionnaire	At Month 24	Evolution of the Mental Component Score of the SF-36 questionnaire between inclusion and the end of the study period (two years).
Evolution of of the EQ-5D-5L score	at Day 0, Month 12 and Month 24 follow-up visit	Evolution of of the EQ-5D-5L score throughout the study, as performed at J0, M12 and M24 follow-up visit (every 12 months).
Evolution of Serum ferritin and serum transferrin saturation	Day 0, Month 6, Month 12, Month 18 and Month 24/follow-up visit	Evolution of Serum ferritin and serum transferrin saturation determined at each follow-up visit (every 6 months).
Occurrence of anaemia	Day 0, Month 6, Month 12, Month 18 and Month 24/follow-up visit	Occurrence of anaemia defined as haemoglobin lower than 11g/dL at any follow-up visit.
Incremental Cost-Effectiveness Ratio	At Month 24	Incremental Cost-Effectiveness Ratio (ICER) defined as the cost for QALY gained in the "transferrin saturation + ferritin" strategy versus "ferritin alone" strategy.

Trial Locations

Locations (12)

CHU Rennes; 🇫🇷 Rennes, France

Hôpital Paul Brousse; 🇫🇷 Villejuif, France

Hopital Avicenne; 🇫🇷 Bobigny, France

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France

CHU Dupuytren; 🇫🇷 Limoges, France

GHBS site du Scorff; 🇫🇷 Lorient, France

GHRMSA - Hôpital Emile Muller; 🇫🇷 Mulhouse, France

CHR Orléans; 🇫🇷 Orléans, France

CH de St Malo; 🇫🇷 Saint-Malo, France

Centre hospitalier Bretagne Atlantique; 🇫🇷 Vannes, France

CH Yves le Foll; 🇫🇷 Saint-Brieuc, France

Hôpital Rangueil; 🇫🇷 Toulouse, France