ferdon: Clinical Evaluation of Iron Treatment Efficiency Among Non-anemic But Iron-deficient Female Blood Donors

• Sponsor: University of Lausanne (Other)
• Overall Status: Completed
• CT.gov ID: NCT00689793
• Collaborator: Pierre Fabre Laboratories (Industry)
• Enrollment: 154
• Location: 1
• Arms: 2
• Duration (Months): 28.9
• Patients Per Site Per Month: 5.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the subjective response of iron substitution (Tardyferon®) on fatigue in women blood donors with a mean serum ferritin < 30ng/ml and to assess variation of ferritin and hemoglobin after a blood donation.

Condition or Disease	Intervention/Treatment	Phase
Fatigue; Iron Deficiency	Drug: Ferrous sulphate; Drug: Placebo	Phase 4

Detailed Description

• Actually, there's no recommendation to check ferritin level in blood donors, even if several studies pointed out the high prevalence of iron deficiency after a blood donation. Furthermore, some clinical trials showed that non-anaemic women with unexplained fatigue may benefit from iron supplementation.

• The purpose of this study is to determine the subjective response of iron substitution (Tardyferon®) on fatigue in women blood donors with a mean serum ferritin < 30ng/ml and to assess variation of ferritin and hemoglobin after a blood donation.

• We will measure blood count, ferritin level and C-reactive protein at the time of the blood donation and then after a week, a month and 3 months.

A week after the blood donation, donors with a ferritin level <30 ng/ml and hemoglobin > 120g/l (non anaemic) will be included in the study and randomised. A one-month iron treatment vs placebo will be introduced. To assess the subjective response on fatigue, the donors will fill in different questionnaires at the time of the blood donation and then after a week, a month and 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clinical Evaluation of Iron Treatment Efficiency Among Non-anemic But Iron-deficient Female Blood Donors : a Randomized Controlled Trial
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1	Drug: Ferrous sulphate; Volunteers will receive 80 mg/day oral ferrous sulphate (Tardyferon®) for four weeks. Visual analogical scales and questionnaires will be performed at day 0 and 30 to quantify fatigue (" Fatigue Severity Scale"). We will also check depression and anxiety symptoms (" Prime MD ") and health survey (" SF-12 "). An evaluation of the menstruation (" Pictorial Bleeding Assessment Chart " of Jansen) will be performed at day 0 to detect a possible hypermenorrhea (appendix 1-4). A physical test will be performed (Chester Step Test) to assess the VO2 max. Every side effect will be written on follow-up notes.; Other Names: Iron treatment Ferrous sulphate treatment Tardyferon Robapharm Fer Sulphate de fer Sulphate ferreux Iron deficiency
Placebo Comparator: 2	Drug: Placebo; Volunteers will receive 1 pill/day oral placebo for four weeks. Visual analogical scales and questionnaires will be performed at day 0 and 30 to quantify fatigue (" Fatigue Severity Scale"). We will also check depression and anxiety symptoms (" Prime MD ") and health survey (" SF-12 "). An evaluation of the menstruation (" Pictorial Bleeding Assessment Chart " of Jansen) will be performed at day 0 to detect a possible hypermenorrhea (appendix 1-4). A physical test will be performed (Chester Step Test) to assess the VO2 max. Every side effect will be written on follow-up notes.; Other Names: Iron treatment Ferrous sulphate treatment Tardyferon Robapharm Fer Sulphate de fer Sulphate ferreux Iron deficiency

Outcome Measures

Primary Outcome Measures

1. Level of Fatigue Before and After Iron Treatment/Placebo, Using a 10 Point Visual Analogue Scale. [baseline and 4 weeks]

   The level of fatigue perceived at baseline and after 4 weeks was scored on a 10-point visual analogue scale ranging from "no fatigue=0" to "very severe fatigue=10".

Secondary Outcome Measures

1. Hemoglobin Variation Before and After Treatment vs Placebo [baseline and 4 weeks]

   The level of hemoglobin measured 4 weeks after randomization

2. Ferritin Change Before and After 4 Weeks of Treatment/Placebo [baseline and 4 weeks]

   Level of ferritin measured 4 weeks after randomization

3. Aerobic Capacity Using an Indirect Measurement of VO2Max : Chester Step Test [baseline and 4 weeks]

   Subjects were asked to step on to and off a 20cm step at a rate set by a metronome. Step rate increased gradually until subject reached her submaximal predicted heart rate.

4. Response of Iron Supplementation on Mental Disorder [baseline and 4 weeks]

   Depression was assessed using the Prime-MD Patient Health Questionnaire (PHQ-9), self-administered by the subject.Diagnosis of depression syndrom was made scoring results of the nine item (range : 0-3). A score >15 (range of total overall scale:0-27) was considered as a depression syndrome. The outcome measure is the number the donors with a depression syndrome at baseline who had a positive response (total score= or <15) after placebo or treatment.

5. Adherence to Treatment. [4 weeks]

   Adherence to treatment was calculated as the number of days with at least one opening of the electronic device divided by the total number of monitored days. The device was a MEMS (Medication Event Monitoring System,AARDEX, Europe, Switzerland)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• women

• aged 18 - 50

• eligible for a blood donation

Exclusion Criteria:

• men

• age below 18 or above 50

• not eligible for a blood donation (according to the blood donation eligibility guidelines of the Swiss Red Cross)

• hemochromatosis, psychiatric / thyroid / hepatic / rheumatismal / kidney or cardiopulmonary diseases that can cause fatigue

• intestinal disease or medical treatment that can perturb iron absorption and/or excretion

• donors with mental disorder or psychiatric disease that are unable to give consent

• acute or chronic inflammation

• diabetes and pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Ambulatory Care and Community Medicine, University Hospitals of Lausanne	Lausanne	Bugnon 44	Switzerland	1011

Sponsors and Collaborators

• University of Lausanne
• Pierre Fabre Laboratories

Investigators

• Principal Investigator: Bernard Favrat, MD PD, Department of Amulatory Care and Community Medicine, University of Lausanne
• Study Chair: Baptiste Pedrazzini, MD, Department of Amulatory Care and Community Medicine, University of Lausanne
• Study Chair: Jacques Cornuz, Prof, Department of Amulatory Care and Community Medicine, University of Lausanne
• Study Chair: Alain Pécoud, Prof, Department of Amulatory Care and Community Medicine, University of Lausanne
• Study Chair: Sophie Waldvogel, MD, Blood Transfusion Department, University Hospitals of Lausanne
• Study Chair: Jean-Daniel Tissot, Prof, Blood Transfusion Department, University Hospitals of Lausanne

Study Documents (Full-Text)

None provided.

More Information

Publications

• BEUTLER E, LARSH SE, GURNEY CW. Iron therapy in chronically fatigued, nonanemic women: a double-blind study. Ann Intern Med. 1960 Feb;52:378-94.
• Brownlie T 4th, Utermohlen V, Hinton PS, Giordano C, Haas JD. Marginal iron deficiency without anemia impairs aerobic adaptation among previously untrained women. Am J Clin Nutr. 2002 Apr;75(4):734-42.
• Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet. 1996 Oct 12;348(9033):992-6.
• Buckley JP, Sim J, Eston RG, Hession R, Fox R. Reliability and validity of measures taken during the Chester step test to predict aerobic power and to prescribe aerobic exercise. Br J Sports Med. 2004 Apr;38(2):197-205.
• Gandek B, Ware JE, Aaronson NK, Apolone G, Bjorner JB, Brazier JE, Bullinger M, Kaasa S, Leplege A, Prieto L, Sullivan M. Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol. 1998 Nov;51(11):1171-8.
• Janssen CA. A simple visual assessment technique to discriminate between menorrhagia and normal menstrual blood loss. Eur J Obstet Gynecol Reprod Biol. 1996 Dec;70(1):21-2. Review.
• Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989 Oct;46(10):1121-3.
• Maghsudlu M, Nasizadeh S, Toogeh GR, Zandieh T, Parandoush S, Rezayani M. Short-term ferrous sulfate supplementation in female blood donors. Transfusion. 2008 Jun;48(6):1192-7. doi: 10.1111/j.1537-2995.2007.01671.x. Epub 2008 Mar 17.
• Magnussen K, Bork N, Asmussen L. The effect of a standardized protocol for iron supplementation to blood donors low in hemoglobin concentration. Transfusion. 2008 Apr;48(4):749-54. doi: 10.1111/j.1537-2995.2007.01601.x. Epub 2008 Jan 8.
• Newman B. Iron depletion by whole-blood donation harms menstruating females: the current whole-blood-collection paradigm needs to be changed. Transfusion. 2006 Oct;46(10):1667-81. Review.
• Newman BH, Roth AJ. Estimating the probability of a blood donation adverse event based on 1000 interviewed whole-blood donors. Transfusion. 2005 Nov;45(11):1715-21.
• Patterson AJ, Brown WJ, Powers JR, Roberts DC. Iron deficiency, general health and fatigue: results from the Australian Longitudinal Study on Women's Health. Qual Life Res. 2000;9(5):491-7.
• Patterson AJ, Brown WJ, Roberts DC. Dietary and supplement treatment of iron deficiency results in improvements in general health and fatigue in Australian women of childbearing age. J Am Coll Nutr. 2001 Aug;20(4):337-42.
• Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999 Nov 10;282(18):1737-44.
• Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, Bischoff T, de Vevey M, Studer JP, Herzig L, Chapuis C, Tissot J, Pécoud A, Favrat B. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003 May 24;326(7399):1124.

• Responsible Party: Bernard Favrat, MD, University of Lausanne
• ClinicalTrials.gov Identifier: NCT00689793
• Other Study ID Numbers: Iron-0508-PMU
• First Posted: Jun 4, 2008
• Last Update Posted: Feb 15, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Bernard Favrat, MD, University of Lausanne: Fatigue; Blood donation; Iron deficiency; Ferrous sulphate; Donation; Donors; Iron; Ferritin; Hemoglobin; Anemia; Anaemia; Haemoglobin; Don; Women blood donors
• Additional relevant MeSH terms: Anemia, Iron-Deficiency; Fatigue; Iron

Study Results

Participant Flow

Recruitment Details	Premopausal female blood donors coming spontaneously to the donation center, were asked to participated to this study. After agreement an informed consent was signed.
Pre-assignment Detail	One week after whole blood donation, participants were randomized if they were not anemic and their ferritin level was < or = 30 ng/mL.

Arm/Group Title	Oral Treatment of Iron	Placebo
Arm/Group Description	One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily) during one month.	One week after donation, donors self-administered on pill of placebo (daily), during one month.
Period Title: Overall Study
STARTED	78	76
COMPLETED	74	71
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Oral Treatment of Iron	Placebo	Total
Arm/Group Description	One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily) during one month.	One week after donation, donors self-administered on pill of placebo (daily), during one month.	Total of all reporting groups
Overall Participants	78	76	154
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	78 100%	76 100%	154 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.9 (8.4)	30.7 (8.8)	31.6 (8.7)
Sex: Female, Male (Count of Participants)
Female	78 100%	76 100%	154 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Switzerland	78 100%	76 100%	154 100%

Outcome Measures

1. Primary Outcome

Title	Level of Fatigue Before and After Iron Treatment/Placebo, Using a 10 Point Visual Analogue Scale.
Description	The level of fatigue perceived at baseline and after 4 weeks was scored on a 10-point visual analogue scale ranging from "no fatigue=0" to "very severe fatigue=10".
Time Frame	baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

The sample size for randomized volunteers was calculated using a two-sample comparison of means to detect a one point difference in the visual analogical scale (first outcome).

Arm/Group Title	Oral Treatment of Iron	Placebo
Arm/Group Description	One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily) during one month.	One week after donation, donors self-administered one pill of placebo (daily), during 4 weeks.
Measure Participants	74	71
Mean (Standard Deviation) [centimeter]	3.4 (2.4)	3.5 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Treatment of Iron
	Comments	The null hypothesis was that there was no difference in fatigue VAS scores between the treatment and placebo groups at 4 weeks
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments	Significant level of treatment effect was set at p<0.05
	Method	Regression, Linear
	Comments	Level of fatigue at four weeks:dependant variable. Group allocation and level of fatigue at baseline: independant variables.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1
	Confidence Interval	(2-Sided) 95%; 0 to 10
	Parameter Dispersion	Type: Standard Deviation; Value: 2.5
	Estimation Comments

2. Secondary Outcome

Title	Hemoglobin Variation Before and After Treatment vs Placebo
Description	The level of hemoglobin measured 4 weeks after randomization
Time Frame	baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

The number of participants was calculated according to the primary outcome.

Arm/Group Title	Oral Treatment of Iron	Placebo
Arm/Group Description	One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily), during one month.	One week after donation, donors self-administered on pill of placebo (daily), during one month.
Measure Participants	74	71
Mean (Standard Deviation) [g/L]	135 (6.7)	130 (5.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Treatment of Iron, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Regression, Linear
	Comments	Hemoglobin value at four weeks : dependant variable. Group allocation and hemoglobin value at baseline : independant variables.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3
	Confidence Interval	() 95%; 0 to 10
	Parameter Dispersion	Type: Standard Deviation; Value: 6.5
	Estimation Comments

3. Secondary Outcome

Title	Ferritin Change Before and After 4 Weeks of Treatment/Placebo
Description	Level of ferritin measured 4 weeks after randomization
Time Frame	baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Treatment of Iron	Placebo
Arm/Group Description	One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily) during one month.	One week after donation, donors self-administered on pill of placebo (daily), during one month.
Measure Participants	74	71
Mean (Standard Deviation) [ng/mL]	28.0 (9.8)	12.9 (8.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Treatment of Iron, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Regression, Linear
	Comments	Ferritin level at 4 weeks : dependant variable. Group allocation and ferritin level at baseline: independant variables.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15
	Confidence Interval	(2-Sided) 95%; 0 to 30
	Parameter Dispersion	Type: Standard Deviation; Value: 8
	Estimation Comments

4. Secondary Outcome

Title	Aerobic Capacity Using an Indirect Measurement of VO2Max : Chester Step Test
Description	Subjects were asked to step on to and off a 20cm step at a rate set by a metronome. Step rate increased gradually until subject reached her submaximal predicted heart rate.
Time Frame	baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Treatment of Iron	Placebo
Arm/Group Description	One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily) during one month.	One week after donation, donors self-administered on pill of placebo (daily), during one month.
Measure Participants	74	71
Mean (Standard Deviation) [mLO2/kg/min]	40.5 (14.5)	40.1 (17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Treatment of Iron, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Regression, Linear
	Comments	Aerobic capacity at 4 weeks : dependant variables. Group allocation and aerobic capacity at baseline : independant variable.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3
	Confidence Interval	(2-Sided) 95%; 0 to 6
	Parameter Dispersion	Type: Standard Deviation; Value: 3
	Estimation Comments

5. Secondary Outcome

Title	Response of Iron Supplementation on Mental Disorder
Description	Depression was assessed using the Prime-MD Patient Health Questionnaire (PHQ-9), self-administered by the subject.Diagnosis of depression syndrom was made scoring results of the nine item (range : 0-3). A score >15 (range of total overall scale:0-27) was considered as a depression syndrome. The outcome measure is the number the donors with a depression syndrome at baseline who had a positive response (total score= or <15) after placebo or treatment.
Time Frame	baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Number of participant was set according the primary outcome.

Arm/Group Title	Oral Treatment of Iron	Placebo
Arm/Group Description	One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily) during one month.	One week after donation, donors self-administered on pill of placebo (daily), during one month.
Measure Participants	74	71
Number [participants]	3 3.8%	4 5.3%

6. Secondary Outcome

Title	Adherence to Treatment.
Description	Adherence to treatment was calculated as the number of days with at least one opening of the electronic device divided by the total number of monitored days. The device was a MEMS (Medication Event Monitoring System,AARDEX, Europe, Switzerland)
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Treatment of Iron	Placebo
Arm/Group Description	One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily) during one month.	One week after donation, donors self-administered on pill of placebo (daily), during one month.
Measure Participants	74	71
Mean (Standard Deviation) [percentage of day]	96 (16.7)	96 (14.2)

Adverse Events

Time Frame	adverse events were reported during the 4 weeks of treatment/placebo
Arm/Group Title	Oral Treatment of Iron		Placebo
Arm/Group Description	One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily) during one month.		One week after donation, donors self-administered on pill of placebo (daily), during one month.
All Cause Mortality
	Oral Treatment of Iron		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oral Treatment of Iron		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		0/71 (0%)
Other (Not Including Serious) Adverse Events
	Oral Treatment of Iron		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/74 (39.2%)		11/71 (15.5%)
Gastrointestinal disorders
gastro-intestinal events	25/74 (33.8%)	25	11/71 (15.5%)	11
General disorders
other events (not serious)	6/74 (8.1%)	6	3/71 (4.2%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.