Clinical Trials Register

Summary
EudraCT Number:	2014-002827-87
Sponsor's Protocol Code Number:	FITTRIAL
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-10-07
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-002827-87

A.3

Full title of the trial

Multicenter randomized controlled trial comparing Ferric(III)carboxymaltose infusion with oral iron suppletion in the treatment of preoperative anaemia in colorectal cancer patients

STUDIO MULTICENTRICO RANDOMIZZATO PER CONFRONTARE L’EFFICACIA DELL’INFUSIONE PRE-OPERATORIA DI FERRO(III)-CARBOSSIMALTOSIO IN CONFRONTO ALLA SOMMINISTRAZIONE ORALE DI FERRO NEL TRATTAMENTO DELL’ANEMIA PERI-OPERATORIA IN PAZIENTI CON CANCRO COLO-RETTALE

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Comparison between Ferric(III)carboxymaltose intravenous infusion and oral iron fumarate administration for the treatment of pre-operative anemia in patients diagnosed with colorectal cancer

Comparazione dell’infusione di Ferro carbossimaltosio e amministrazione orale di ferro fumarato per il trattamento dell’anemia pre-operatoria in pazienti affetti da cancro colo-rettale.

A.3.2

Name or abbreviated title of the trial where available

Trial Comparing Ferric(III)Carboxymaltose Infusion With Oral Iron Suppletion as Treatment of Anaemia

Studio di confronto tra infusione di ferro carbossimaltosio e integrazione orale di ferro per il tra

A.4.1

Sponsor's protocol code number

FITTRIAL

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ACADEMIC MEDICAL CENTRE AMSTERDAM
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ACADEMIC MEDICAL CENTRE AMSTERDAM
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS Istituto Clinico Humanitas
B.5.2	Functional name of contact point	Unità Operativa Chirurgia del Colon
B.5.3	Address:
B.5.3.1	Street Address	Via Manzoni, 56
B.5.3.2	Town/ city	Rozzano (MI)
B.5.3.3	Post code	20089
B.5.3.4	Country	Italy
B.5.4	Telephone number	0282247776
B.5.6	E-mail	annalisa.maroli@humanitas.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	FERRO GRAD FOLIC - COMPRESSE A RILASCIO PROLUNGATO 20 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	TEOFARMA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ferro-solfato
D.3.2	Product code	[Ferro-solfato]
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FERRO
D.3.9.2	Current sponsor code	901128138
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	105
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Ferinject
D.2.1.1.2	Name of the Marketing Authorisation holder	Vifor Pharma Italia s.r.l.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ferinject
D.3.2	Product code	[Ferinject]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FERRO(III)-CARBOSSIMALTOSIO
D.3.9.2	Current sponsor code	040251035
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

perioperative anaemia in colorectal cancer patients

ANEMIA PERI-OPERATORIA IN PAZIENTI CON CANCRO COLO-RETTALE

E.1.1.1

Medical condition in easily understood language

Pre-operative anemia in patients diagnosed with colorectal cancer.

Anemia pre-operatoria in pazienti affetti da cancro del colon retto.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10002272
E.1.2	Term	Anemia
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the percentage of patients with normalization of Hb-level (> 12 g/dl (7.5 mmol/l) for women and > 13 g/dl (8 mmol/l) for men after intravenous versus oral iron therapy in patients undergoing curative surgery for colorectal carcinoma.

Determinare l’efficacia dell’infusione di ferro intra-venosa in confronto alla somministrazione orale standard di ferro in sede pre-operatoria nel contrastare l’anemia pre-operatoria in pazienti affetti da cancro colo-rettale.

E.2.2

Secondary objectives of the trial

1) To analyse the effect of preoperative iron therapy (intravenous versus oral) on postoperative morbidity, length of stay, amount of blood transfusions needed and quality of life and fatigue scores.
2) To determine the cost effectiveness of preoperative intravenous iron substitution in comparison with oral substitution.

Confrontare i gruppi di studio sulla base dell’incidenza di complicanze post-operatorie, qualità della vita e costi medici.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- M0-stage Colorectal carcinoma
- Laparoscopic or open segmental colonic resection or (low) anterior resection
- Iron deficiency anaemia: Hb <7,5 mmol/l (12 g/dl) for women and Hb < 8 mmol/l (13 g/dl) for men and TSAT<20%
- Patient is not in need for blood transfusion according to physicians opinion or national guideline (age < 25 years : 3.5-4.5 mmol/l, age = 25-50 years: 4.0-5.0 mmol/l, age = 50-70 years : 5.5 mmol/l, age > 70 year: 6.0 mmol/l)
- Age 18 or older
- Written informed consent for study participation

• Pazienti di entrambi i sessi, di età maggiore di 18 anni;
• Pazienti che abbiano firmato il Consenso Informato;
• Pazienti indicati a chirurgia colo-rettale (laparoscopia o laparotomica) di elezione curativa;
• Pazienti con anemia sideropenica (Hb<13 g/dL per gli uomini e Hb<12 g/dL per le donne, TSAT<20%);
• Pazienti per cui non sia necessaria una trasfusione, in accordo con la decisione medica e le linee guida internazionali;
• Pazienti con stadiazione pre-operatoria M0.

E.4

Principal exclusion criteria

- Palliative surgery / metastasized disease
- Received blood transfusion within one month before screening
- Serum ferritin = 800 µg/L
- Pregnancy
- Preoperative chemoradiation (Short course radiotherapy (5x5 Gy) = no exclusion)
- Contraindication for the use of ferric(III)carboxymaltose or oral iron suppletion (ferrofumarate or ferrous sulphate)
- ASA classification > 3
- Use of erythropoietin stimulating agents within three months before screening
- Chronic kidney disease (GFR < 30ml/min/m)
- Myelodysplastic syndrome
- Elevated liver enzymes (more than three times normal value)
- Hereditary Hemochromatosis
- Thalassemia
- Haemolytic anaemia/ chronic haemolysis

• Pazienti incapaci di fornire il Consenso Informato scritto;
• Pazienti di età inferiore ai 18 anni;
• Pazienti incinte o in allattamento;
• Pazienti indicati a chirurgia palliativa;
• Pazienti con evidenza pre-operatoria di metastasi distali;
• Pazienti che abbiano ricevuto una trasfusione nei 30 giorni precedenti alla randomizzazione;
• Ferritina sierica > 800 µg/L;
• Pazienti che abbiano subito chemioradioterapia neo-adiuvante;
• Controindicazioni note all’utilizzo di ferro(III)-carbossimaltosio;
• Pazienti con classificazione ASA>3;
• Utilizzo di agenti stimolanti eritropoietina nei tre mesi precedenti la randomizzazione;
• Sindrome mielodisplastica;
• Malattie renali croniche;
• Enzimi epatici elevati (più di tre volte rispetto ai limiti);
• Emocromatosi ereditaria;
• Talassemia;
• Anemia emolitica o emolisi cronica.

E.5 End points

E.5.1

Primary end point(s)

- Percentage of patients with normalization of Hb-level from start treatment until surgery. (Hb >12g/dl (7.5mmol/L) for women and Hb >13 g/dl (8.0mmol/L) for men)

Valutare la percentuale di pazienti con livelli di emoglobina normalizzati in seguito a trattamento.

E.5.1.1

Timepoint(s) of evaluation of this end point

4 weeks after surgery

4 settimane dopo l’intervento chirurgico.

E.5.2

Secondary end point(s)

- Change in morbidity score (Comprehensive Complication index).
- Change in HB from baseline prior to surgery, at day 1, and at 1,4, 8 and 12 weeks postoperatively.
- Time needed to achieve normalization of Hb-level
- Change in baseline in other iron/haematological parameters (i.e. TSAT, ferritin, CRP) pre-operatively, at day 1, and at 1, 4 and 8 and 12 weeks post-operatively.
- Change from baseline in health-related QoL (EQ-5D, EORTC-C30, EORTC -CR29 iMCQ & iPCQ) pre-operatively, and at 4 weeks and 6 months post-operatively.
- Change from baseline in fatigue (BFI) pre-operatively and at 2, 4 and 12 weeks post-operatively.
- Amount of blood transfusions needed.
- Relation between anaemia and Glasgow Prognostic Score (derived from CRP and Albumin).
- Relation between CRP and degree of anaemia.
- Length of stay.
- Gastro-intestinal intolerance of study drug treatment.
- Cost-effectiveness of intravenous iron treatment compared to oral.

Valutare l’effetto della terapia ferrica di supporto sull’incidenza di complicanze post-chirurgiche.

E.5.2.1

Timepoint(s) of evaluation of this end point

4 weeks after surgery

4 settimane dopo l’intervento chirurgico.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

198

F.4.2.2

In the whole clinical trial

198

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Best standard treatment.

La migliore cura standard.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-06-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-02-27

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