Condition category
Nutritional, Metabolic, Endocrine
Date applied
14/02/2010
Date assigned
17/03/2010
Last edited
30/06/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Christian Breymann

ORCID ID

Contact details

Gynakologie Geburtshilfe Seefeld
Seefeldstrasse
214
Zurich
CH-8008
Switzerland
+41 (0)43 818 59 68
breymann@ggs-zh.ch

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Effect of intravenous iron versus placebo on exhaustion symptoms in non-anaemic premenopausal women with low ferritin levels

Acronym

FERRIM

Study hypothesis

Administration of intravenous iron to non-anemic pre-menopausal women with low serum ferritin (S-ferritin) levels will improve physical and mental performance

Please note that as of 24/05/10 a brief description of the study results has been added to this record. More details are available in the interventions section below.

Ethics approval

Both local and central ethical approval was obtained prior to study start - study conducted according to Swissmedic, ICH GCP guidelines and Declaration of Helsinki

Study design

Randomised multicentre double blind placebo controlled superiority study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact Lise Riopel [lise.riopel@viforpharma.com] to request a patient information sheet.

Condition

Reduced physical and mental performance in pre-menopausal women

Intervention

Venofer®, (iron sucrose injection) is an aqueous complex of polynuclear iron (III)- hydroxide in sucrose for intravenous use. Patients received either 2 infusions each containing 200 mg iron [III]-hydroxide sucrose (Venofer®) or 2 infusions of 200 ml 0.9% saline (placebo) administered over a minimum period of 10 minutes each week for the first two weeks of the trial. Each patient received a total of 4 infusions representing a total of 800 mg of iron in the Venofer® treated group. Patients were followed for total period of 3 months.

Added 24/05/10:
Statistical methods:
For description of the distribution medians and range were used. For analysis of differences of distribution of investigated parameters between Venofer and placebo groups, a non parametric test (Mann- Whitney U-Test) was used. Both types of analyses were performed, because deviations from normal distribution were found for primary objective variables, most items are categorically scaled parameters.

Study Results:
1. Efficacy:
Difference from baseline in median Brief Fatigue Inventory (BFI) score between the treatment groups was not statistically significant but suggest a trend toward a greater improvement in patients treated with iron sucrose (difference in change BFI: -0.44, p=0.076). There was a significantly (p=0.036) greater improvement in categorized tBFI scores from baseline to Day 42 in patients treated with IV iron sucrose compared to patients treated with placebo There were significant differences between the study groups in some sub-group analyses. Among patients presenting with severe iron deficiency at baseline (defined as TSAT below 20% and serum ferritin below 50 ng/mL or serum ferritin below 15 ng/mL) there was a significantly greater improvement in BFI score at Day 42, in patients treated with IV iron sucrose compared to patients treated with placebo (p=0.026).
There was a significant correlation between the change in fatigue from baseline to Day 42 as measured by the BFI and the change in fatigue as measured by Short Performance Inventory (SPI), a global investigator assessment (r=0.59, p<0.0001).
Patients treated with IV iron sucrose showed a significant increase in serum-ferritin values during the study compared to baseline, and this increase was significantly greater in the IV iron sucrose group compared to the placebo group (p<0.0001).
The results of this study suggest a clinical benefit for patients treated with iron sucrose and warrant further investigation in this area.

2. Safety:
In total, 54 of 89 enrolled patients reported at least one adverse effect (AE) during the clinical study; most of the AEs were mild and unrelated to study medication. Two serious AEs (SAEs) were reported, one in each treatment group. There was one case of appendicitis and one serious traffic accident. Both were unrelated to treatment. Further, there were no clinically relevant abnormal findings in vital signs, physical exams or evaluation of concomitant medication during the study. This suggests that the iron sucrose treatment caused no safety concerns. It can be concluded that the incidence of AEs following iron sucrose administration is low and reflects the safety profile labelled in the SmPC.

Intervention type

Drug

Phase

Not Specified

Drug names

Iron [III]-hydroxide sucrose (Venofer®)

Primary outcome measures

1. Brief Fatigue Inventory (total score = tBFI) assessed at baseline, day 42 and 90
2. Serum ferretin, assessed at baseline, 3rd treatment visit, day 42 and 90

Secondary outcome measures

1. BFI intensity mean score and impairment score, assessed at baseline, day 42 and 90
2. Haematological parameters, assessed at baseline, day 42 and 90
2.1. Hb
2.2. Mean corpuscular volume (MCV)
2.3. Mean corpuscular haemoglobin concentration (MCHC)
2.4. Haematocrit (HCT)
3. Iron status, assessed at baseline, 3rd treatment visit, day 42 and 90
3.1. Serum iron
3.2. Transferrin Saturation (Tsat)
3.3. Transferrin
4. Safety
4.1. Adverse effects
4.2. Physical exam, assessed at day 90
4.3. Body weight and height, assessed at day 90
4.4. Vital signs, assessed at baseline, day 42 and 90
4.5. Creatinine, assessed at baseline
4.6. Alanine Aminotransferase (ALT), assessed at baseline
4.7. Aspartate Aminotransferase (AST), assessed at baseline
4.8. C-Reactive protein (CRP), assessed at baseline, day 42 and 90
5. Concomitant medications

Overall trial start date

21/09/2006

Overall trial end date

07/08/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. Premenopausal, regularly menstruating women
2. Age ≥ 18 years
3. S-ferretin < 50ng/mL
4. Signed informed consent
5. Reduced physical and mental performance (fatigue, depressive mood, dizziness, sleep disturbance, concentration, neck pain, headache) as determined by investigator
6. Adequate contraception

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

100 (50 patients/group)

Participant exclusion criteria

1. Haemoglobin (Hb) level 120 g/L
2. Known mental and physical disorder (cancer, depression)
3. Use of concomitant medication to cause symptoms of fatigue and depression (antidepressive & chemotherapeutic agents, sedatives)
4. Use of iron preparations within previous 4-weeks
5. Active sever infection, inflammation, malignancy
6. C-Reactive Protein (CRP) > 20 mg/mL
7. Thyroid-Stimulating Hormone (TSH) > 4 micro U/mL
8. Use of menstruation depressing gestagens
9. History of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV)
10. Significant cardiovascular disease e.g. unstable angina, New York Heart Association (NYHA) class IV
11. Hypersensitivity to iron sucrose or iron sulphate
12. Pregnancy or lactation
13. Participation in any other therapeutic study in the previous month

Recruitment start date

21/09/2006

Recruitment end date

07/08/2008

Locations

Countries of recruitment

Switzerland

Trial participating centre

Gynakologie Geburtshilfe Seefeld
Zurich
CH-8008
Switzerland

Sponsor information

Organisation

Vifor Pharma, Vifor (International) Ltd (Switzerland)

Sponsor details

Flughofstrasse 61
Glattbrugg
CH-8152
Switzerland
+41 (0)58 851 80 00
clive.burge@viforpharma.com

Sponsor type

Industry

Website

http://www.viforpharma.com

Funders

Funder type

Industry

Funder name

Vifor Pharma, Vifor (International) Ltd. (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21705493

Publication citations

  1. Results

    Krayenbuehl PA, Battegay E, Breymann C, Furrer J, Schulthess G, Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration., Blood, 2011, 118, 12, 3222-3227, doi: 10.1182/blood-2011-04-346304.

Additional files

Editorial Notes