Ferric Carboxymaltose in Type 2 Diabetes Mellitus (T2DM) Patients With Iron Deficiency (CLEVER)

Intravenous Ferric Carboxymaltose for Improvement of Metabolic Parameters and Vascular Function in T2DM-patients With Iron Deficiency

The purpose of this study is to investigate the correlation between HbA1c and iron status in Type 2 Diabetes mellitus patients with iron deficiency by intravenous substitution of iron.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Iron Deficiency
• Intervention / Treatment: Drug: ferric carboxymaltose; Drug: NaCl (0,9%)

• Study Type: Interventional
• Enrollment (Anticipated): 152
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum NRW Ruhr-Universitat Bochum
  • Dresden, Germany, 01307
    • Studienzentrum Professor Hanefeld Abakus Büropark
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover Klinisches Forschungszentrum CRC
  • Heidelberg, Germany, 69115
    • Diabetesinstitut Heidelberg
  • Nordrhein-Westfalen
    • Herne, Nordrhein-Westfalen, Germany, 32545
      • Gemeinschaftspraxis Dres. Grüneberg, Mehring, Stude
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Univesitätsklinikum Carl Gustav Carus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

T2DM patients with diagnosis of ID defined as follows:

• serum ferritin <150 ng/mL or TSAT <25% if Hb < 14 g/dL serum ferritin <100 ng/mL or TSAT <20% if Hb ≥ 14 g/dL and ≤ 15g/dL]
• HbA1c: ≥ 6.5 to < 8.5 %
• Age > 18 years
• Written informed consent has been obtained.

Exclusion Criteria:

• Continuous subcutaneous insulin infusion (CSII)
• thalassaemia
• Hb > 15 g/dL (> 9,31 mmol/L)
• Change of HbA1c of more than ±0,3 % within the last 3 months.
• known sensitivity to ferric carboxymaltose
• history of acquired iron overload
• History of erythropoietin stimulating agent, i.v. iron therapy, and/or blood transfusion in previous 12 weeks prior to randomisation
• History of oral iron therapy at doses ≥ 100 mg/day 1 week prior to randomisation. Note: Ongoing oral use of multivitamins containing iron < 75 mg/day is permitted.
• Body weight ≤ 40 kg
• CRP > 15 mg/L
• Chronic liver disease (including known active hepatitis) and/or screening alanine transaminase (ALAT) or aspartate transaminase (ASAT) > 3 x ULN (upper limit of the normal range).
• Subjects with known hepatitis B surface antigen positivity and/or Hepatitis C virus ribonucleic acid positivity.
• Vitamin B12 and/or serum folate deficiency. If deficiency corrected subject may be rescreened for inclusion.
• Subjects with known seropositivity to human immunodeficiency virus.
• Clinical evidence of current malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia.
• Currently receiving systemic chemotherapy and/or radiotherapy.
• Renal dialysis (previous, current or planned within the next 6 months).
• Renal function GFR < 30 mL/min/ 1.73m2 (severe)
• Unstable angina pectoris as judged by the Investigator; severe valvular or left ventricular outflow obstruction disease needing intervention; atrial fibrillation/flutter with a mean ventricular response rate at rest >100 beats per minute.
• Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack or stroke within the last 3 months prior to randomisation.
• Coronary-artery bypass graft, percutaneous intervention (e.g., cardiac, cerebrovascular, aortic; diagnostic catheters are allowed) or major surgery, including thoracic and cardiac surgery, within the last 3 months prior to randomisation.
• Patients with a polyneuropathy without ischemia.
• Subject of child-bearing potential who is pregnant (e.g., positive human chorionic gonadotropin test) or is breast feeding.
• Any subject not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.
• Participation in other interventional trials
• Female subject of child-bearing potential who is pregnant (e.g., positive human chorionic gonadotropin test) or is breast feeding.
• Failure to use highly-effective contraceptive methods
• Persons with any kind of dependency on the investigator or employed by the sponsor or investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ferric carboxymaltose; Dose: according to SmPC; Duration: 12 weeks; Frequency: at week 1 and again at week 5 (if again indicated according to principal inclusion criteria); Application: intravenous	Drug: ferric carboxymaltose; Dose:according to SmPC Duration: 12 weeks; Frequency: at week 1 and again at week 5 (if again indicated according to principal inclusion criteria); Application: intravenous; Other Names: Ferinject (marketing authorization number: 66227.00.00)
PLACEBO_COMPARATOR: NaCl (0,9%); Duration: 12 weeks; Frequency: at week 1 and again at week 5 (if again indicated according to principal inclusion criteria); Application: intravenous	Drug: NaCl (0,9%); Duration: 12 weeks; Frequency: at week 1 and again at week 5 (if again indicated according to principal inclusion criteria); Application: intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction in HBA1c-levels	reduction of HbA1c from week 1 (baseline) to week 13	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
improvement of haematological and iron status	Hb, MCV, MCH, hypochromic cells, reticulocyte Hb content, ferritin, transferrin, transferrin saturation (TSAT), sTFR, iron, hepcidin	12 weeks
improvement in quality of life	potential clinical improvement and improvement in quality of life (EQ5D) of patients with ID T2DM	12 weeks
Improvement of metabolic status	measurement of fasting glucose, fructosamine	12 weeks
reliability of HbA1c-measurements	measurement of HbA1c in week 0; 5 and 13	12 weeks
improvement in vascular function	Improvement in vascular function on the basis of the biomarker ADMA serum level	12 weeks
Change in used insulin dosage during study	Change in used insulin dosage during study (via patient diary)	12 weeks

Collaborators and Investigators

• Sponsor: GWT-TUD GmbH
• Collaborators: Vifor Pharma
• Investigators: Principal Investigator: Christoph Schindler, MD, on behalf of GWT

Publications and helpful links

General Publications

• Schindler C, Birkenfeld AL, Hanefeld M, Schatz U, Kohler C, Gruneberg M, Tschope D, Bluher M, Hasslacher C, Bornstein SR. Intravenous Ferric Carboxymaltose in Patients with Type 2 Diabetes Mellitus and Iron Deficiency: CLEVER Trial Study Design and Protocol. Diabetes Ther. 2018 Feb;9(1):37-47. doi: 10.1007/s13300-017-0330-z. Epub 2017 Nov 13. Erratum In: Diabetes Ther. 2018 Dec 6;:

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ACTUAL): October 1, 2018
• Study Completion (ACTUAL): April 1, 2019

Study Registration Dates

• First Submitted: January 3, 2012
• First Submitted That Met QC Criteria: January 16, 2012
• First Posted (ESTIMATE): January 20, 2012

Study Record Updates

• Last Update Posted (ACTUAL): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Diabetes; iron deficiency
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 2; Anemia, Iron-Deficiency
• Other Study ID Numbers: CLEVER-2011; 2011-005224-18 (EUDRACT_NUMBER)