Pilot Study: Randomized, Placebo-controlled Comparator Trial of IV vs Oral Iron Treatment of RLS With IDA. (IVOR-IDA)

NCT ID: NCT02499354

Last Updated: 2024-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2022-05-31

Brief Summary

The purpose of the study is to determine the relative effect size of standard IV and oral iron treatment of RLS with Iron deficiency anemia (IDA) and to determine the time course of treatment response.

Detailed Description

The restless legs syndrome (RLS) (also known as Willis Ekbom Disease) occurs in about 1/3rd of patients with iron deficiency anemia (IDA). Treatment correcting the IDA is expected to also be effective for reducing or eliminating the RLS with IDA. Two accepted treatments for IDA (oral ferrous sulfate, intravenous ferumoxytol) will be compared for efficacy and speed to response for treatment of RLS occurring with IDA (RLS-IDA). In this study 70 RLS-IDA patients will be randomly assigned 35 each to oral or IV iron treatment using double-blind procedures. Primary outcome with be determined at 6 weeks of treatment with a follow-up at 12 months after treatment. Non-responders at 6 weeks after treatment may, if they qualify, have an open-label IV iron treatment and they will be followed with the same evaluations used after the first set of IV iron treatments.

Both oral and IV iron are considered standard treatments for IDA. These same treatments also reduce RLS symptoms. The treatment doses are those accepted for treatment of RLS and also appropriate for treatment for RLS-IDA. Choosing doses equivalent to those for the treatment of RLS without IDA will allow a comparison with that literature. The investigators will therefore use for oral iron ferrous sulfate 325mg taken twice a day matching the dose used in the study of oral iron treatment for RLS without anemia. For IV iron investigators will use ferumoxytol, provided by the sponsor, two doses of 510 mg spaced 2 to 7 days apart. This is the FDA approved dose for treatment of IDA with end stage renal disease.

The study is a randomized, comparative open label study to evaluate effect size and time course of treatment response for RLS-IDA over 6 weeks with a 46-week follow-up extension. Two medications and placebos will be used, as described above, with equal random assignment to both groups.

Conditions

Restless Legs Syndrome; Iron Deficiency Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Oral Iron

Ferrous Sulfate 325mg (oral) tabs morning and evening

Group Type: ACTIVE_COMPARATOR

Ferrous sulfate

Intervention Type: DRUG

Oral iron, 325 mg tabs taken morning and evening

IV Iron

Ferumoxytol intravenous (IV) 1020 mg - 2 vials of 510 mg (IV push, 2-3 mins) each given 2-7 days apart

Group Type: ACTIVE_COMPARATOR

Ferumoxytol intravenous

Intervention Type: DRUG

IV iron, 2 vials of 510 mg given 2-7 days apart

Interventions

Ferumoxytol intravenous

IV iron, 2 vials of 510 mg given 2-7 days apart

Intervention Type: DRUG

Ferrous sulfate

Oral iron, 325 mg tabs taken morning and evening

Intervention Type: DRUG

Other Intervention Names

IV iron; Oral iron

Eligibility Criteria

Inclusion Criteria

• Diagnosis of RLS based on questionnaire and confirmed by Hopkins telephone Diagnostic Interview conducted by investigators or clinicians part of the study.
• Iron deficiency anemia defined as ID either ferritin <20 mcg/l, Tsat <19%, anemia Hgb <13 for both males and females.
• Willingness to use contraceptive to avoid pregnancy: Women have to be surgically sterile, post-menopausal, or use one of the following contraceptives during the whole study period and after the study has ended for at least 5 times plasma biological half-life of the investigational medicinal product: intrauterine devices or hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release).
• Willingness to participate and signing the informed consent form.

Exclusion Criteria

• Iron overload or disturbances in utilization of iron (e.g. haemochromatosis and haemosiderosis)
• Decompensated liver cirrhosis or active hepatitis (ALAT > 3 times upper limit of normal)
• Serum ferritin > 500 ng/mL or transferrin saturation >40%
• Active acute or chronic infections (assessed by clinical judgement that may be indicated by White Blood Cells (WBC) and C-Reactive Protein (CRP) when these are available)
• Rheumatoid arthritis with symptoms or signs of active inflammation
• Pregnant and nursing women
• History of multiple allergies
• Known hypersensitivity to parenteral or oral iron or any excipients in the drug products
• Previous IV iron treatment for RLS
• Other iron treatment or blood transfusion within 4 weeks prior to the screening or treatment visit
• Planned elective surgery during the study
• Current (past 4 weeks) use of drugs that treat RLS, e.g. opioids, alpha-2-delta anti-depressants, dopaminergics (dopamine promoters, dopamine antagonists/blockers)
• Any other medical condition that, in the opinion of Investigator, may cause the subject to be unsuitable for the completion og the study or place the subject at potential risk from being in the study, e.g. a malignancy, uncontrolled hypertension, unstable ischemic heart disease, or uncontrolled diabetes mellitus.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AMAG Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Auerbach Hematology Oncology Associates P C

OTHER

Sponsor Role: lead

Responsible Party

Michael Auerbach MD

Dr. Michael Auerbach

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Auerbach, MD

Role: PRINCIPAL_INVESTIGATOR

Auerbach Hematology and Oncology Associates, PC

Locations

Auerbach Hematology Oncology Assoc

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IVOR-IDA

Identifier Type: -

Identifier Source: org_study_id