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

Type 2 Diabetes Mellitus Clinical Trial

— CLEVER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01513369
• Other study ID #: CLEVER-2011
• Secondary ID: 2011-005224-18
• Status: Completed
• Phase: Phase 3
• Start date: August 2012
• Est. completion date: April 2019

Study information

• Verified date: February 2021
• Source: GWT-TUD GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: April 2019
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Iron Deficiency
• Type 2 Diabetes Mellitus

Intervention

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
• 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

Locations

Country	Name	City	State
Germany	Herz- und Diabeteszentrum NRW Ruhr-Universität Bochum	Bad Oeynhausen
Germany	Studienzentrum Professor Hanefeld Abakus Büropark	Dresden
Germany	Univesitätsklinikum Carl Gustav Carus	Dresden	Sachsen
Germany	Medizinische Hochschule Hannover Klinisches Forschungszentrum CRC	Hannover
Germany	Diabetesinstitut Heidelberg	Heidelberg
Germany	Gemeinschaftspraxis Dres. Grüneberg, Mehring, Stude	Herne	Nordrhein-Westfalen

Sponsors (2)

Lead Sponsor	Collaborator
GWT-TUD GmbH	Vifor Pharma

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	reduction in HBA1c-levels	reduction of HbA1c from week 1 (baseline) to week 13	12 weeks
Secondary	improvement of haematological and iron status	Hb, MCV, MCH, hypochromic cells, reticulocyte Hb content, ferritin, transferrin, transferrin saturation (TSAT), sTFR, iron, hepcidin	12 weeks
Secondary	improvement in quality of life	potential clinical improvement and improvement in quality of life (EQ5D) of patients with ID T2DM	12 weeks
Secondary	Improvement of metabolic status	measurement of fasting glucose, fructosamine	12 weeks
Secondary	reliability of HbA1c-measurements	measurement of HbA1c in week 0; 5 and 13	12 weeks
Secondary	improvement in vascular function	Improvement in vascular function on the basis of the biomarker ADMA serum level	12 weeks
Secondary	Change in used insulin dosage during study	Change in used insulin dosage during study (via patient diary)	12 weeks