Efficacy and Safety of Ferrous Iron on the Prevention of Vascular Cognitive Impairment Among Patients With Cerebral Infarction/TIA (FAVORITE) (FAVORITE)

Efficacy and Safety of Ferrous Iron on the Prevention of Vascular Cognitive Impairment Among Patients With Cerebral Infarction/TIA,FAVORITE

The prevalence of Vascular Cognitive Impairment(VCI) is high in patients after ischemic stroke or transient ischemic attack(TIA) . Effective therapy for the prevention of VCI remains limited. The primary purpose of this study is to evaluate the efficacy and safety of Ferrous iron versus placebo on the prevention of vascular cognitive impairment among patients with ischemic stroke/TIA complicated with Hemoglobin deficiency.

Study Overview

• Status: Unknown
• Conditions: Iron-deficiency; Cerebral Infarction; Dementia, Vascular; TIA; Vascular Cognitive Impairment
• Intervention / Treatment: Drug: Ferrous succinate

Detailed Description

The prevalence of Vascular Cognitive Impairment(VCI) remains 21%~70% among patients after ischemic stroke or TIA. Effective therapy for the prevention of VCI remains limited. Abnormal iron distribution and Systemic iron deficiency may contribute partly to the occurrence of VCI.The primary purpose of this study is to evaluate the efficacy and safety of Ferrous iron versus placebo in reducing the risk of VCI at 1 year in patients with cerebral Infarction/TIA complicated with Hemoglobin deficiency. The secondary purpose is to evaluate the effect of Ferrous iron on the Biological markers of VCI; to evaluate the effect of iron supplement on the outcome(death,stroke recurrence, dependency) of patients with ischemic stroke or TIA complicated with Hemoglobin deficiency at 3 months/1 year after treatment.

This trial is a randomized, double-blind, placebo-controlled, multicenter clinical trial. 1006 patients in 20 centers in China will be enrolled with one of the following situations 1.recent ischemic stroke or TIA (within 3 months) with Fe deficiency （serum ferritin<20µg/L）or Hemoglobin deficiency(<120g/L for female and <130g/L for male).2. Vascular risk factors(hypertension, diabetes mellitus, or dyslipidemia), with multiply lacunar infarctions(≥2) or extensive white matter lesions（Fazekas ≥2） or multiply microhaemorrhage(≥2) showed on CT/Magnetic Resonance(MR) with Fe deficiency （serum ferritin<20µg/L）or Hemoglobin deficiency(<120g/L for female and <130g/L for male).. Patients will be randomly assigned into 2 groups according to the ratio of 1:1:

Ferrous iron therapy (0.2 per day) Placebo Face to face interviews will be made at baseline, 14 (or hospital discharge), 3th month± 7 days and 12th month ± 14 days after randomization.

Primary outcome is defined as prevalence of Vascular Cognition Impairment at 1 year after treatment. Secondary outcomes include all-cause death; ischemic stroke; transient ischemic attack; poor functional outcome (mRS 2-6). Safety outcomes, relating to adverse gastrointestinal reactions and iron overload.

• Study Type: Interventional
• Enrollment (Anticipated): 1006
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Beijing Tiantan Hospital
      • Contact: Jia Qian, doctor; Phone Number: 15810048909; Email: jiaqian1616@163.com
      • Contact: Jia Weili, master; Phone Number: 13120207987; Email: 13120207987@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age :18-80 years old , male or female;
2. one of the following situations: A.recent ischemic stroke or TIA (within 3 months) B. One or more vascular risk factors including hypertension, diabetes mellitus, or dyslipidemia, with multiply lacunar infarctions(≥2) or extensive white matter lesions（Fazekas ≥2） or multiply microhaemorrhage(≥2) showed on CT/MR.
3. Fe deficiency （serum ferritin<20µg/L）or Hemoglobin deficiency(≥60 g/L and <120g/L for female,or ≥60 g/L and <130g/L for male)
4. Signed informed consent.

Exclusion Criteria:

1. CT/MR showed Intracranial haemorrhage or non-cerebral vascular disease (eg. intracranial tumors, multiple sclerosis);
2. Patients who Can not cooperate with the completion of neuropsychological evaluation for Severe hearing impairment, visual impairment, unilateral neglect, or dyskinesia;
3. Patients with Severe anemia with Hemoglobin<60 g/L;
4. Patients with thalassemia, megaloblastic anemia or erythronoclastic anemia.
5. Patients with Mental illness or schizophrenia;
6. Patients who were diagnosed definitely as Alzheimer's disease;
7. Patients having history of taking drugs including Cholinesterase inhibitors、NMDA antagonists、5-hydroxytryptophan receptor antagonists、pyrrolidone and other definite drugs for improving cognition(e.g. donepezil、Galanthamine、Memantine、huperzine A、oxiracetam、aniracetam、piracetam、butyphthalide) within 3 months before randomization；
8. Patients with severe liver or kidney insufficiency(ALT>twofold upper normal limit or Aspartate Aminotransferase>twofold upper normal limit; Cr>1.5 times upper normal limit or Glomerular Filtration Rate<40 ml/min/1.73m2）;
9. Patients with Severe untreated urinary tract infection;
10. Patients with hemochromatosis or hemosiderosis(e.g. Iron lung deposition);
11. Patients with Iron allergy or other contraindications of using Iron；
12. Pregnant or childbearing-age women；
13. Patients who are undergoing experimental drugs or device tests;
14. Patients Unable to finish the follow-up of 3 months or 1 year due to geographical factor or other reasons;
15. Patients or legal representatives refuse to participate.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Ferrous succinate; Ferrous succinate sustained-release tablets（Ferrous succinate 0.2g）1 tablet, Qd, po during or after breakfast, Lasting for 12 weeks.	Drug: Ferrous succinate; Ferrous succinate sustained-release tablets（Ferrous succinate 0.2g）1 tablet, Qd,po during or after breakfast, Lasting for 12 weeks. placebo with almost the same size, color and smell as Ferrous iron will be used with 1 tablet, Qd, po during or after breakfast, Lasting for 12 weeks.; Other Names: Placebo
PLACEBO_COMPARATOR: placebo; placebo with almost the same size, color and smell as Ferrous iron will be used with 1 tablet, Qd, po during or after breakfast, Lasting for 12 weeks.	Drug: Ferrous succinate; Ferrous succinate sustained-release tablets（Ferrous succinate 0.2g）1 tablet, Qd,po during or after breakfast, Lasting for 12 weeks. placebo with almost the same size, color and smell as Ferrous iron will be used with 1 tablet, Qd, po during or after breakfast, Lasting for 12 weeks.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prevalence of vascular cognitive impairment in patients given Ferrous succinate versus placebo	Vascular cognitive impairment will be diagnosed with Montreal Cognitive Assessment(MoCA, range 0-30 scores) <26 scores	1 year after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death	All-cause death	1 year after randomization
Stroke recurrence (including hemorrhagic and ischemic stroke)	Stroke recurrence including hemorrhagic and ischemic stroke	1 year after randomization
Poor functional outcome	The modified Rankin Scale (mRS range 0-6)= 2-6	1 year after randomization
Value of Hemoglobin/serum ferritin/serum Tau/serum Aß	Value of Hemoglobin/serum ferritin/serum Tau/serum Aß	3 months and 1 year after randomization

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Study Chair: Jia Qian, doctor, Beijing Tiantan Hospital; Study Director: Zhang shuting, doctor, West China Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2019
• Primary Completion (ANTICIPATED): October 31, 2021
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: March 23, 2019
• First Posted (ACTUAL): March 27, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2020
• Last Update Submitted That Met QC Criteria: July 10, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: dementia; Clinical Trial; biological markers; TIA; iron deficiency; cerebral infarction; Vascular Cognitive Impairment
• Additional Relevant MeSH Terms: Mental Disorders; Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Brain Ischemia; Cognition Disorders; Stroke; Brain Infarction; Intracranial Arterial Diseases; Intracranial Arteriosclerosis; Leukoencephalopathies; Infarction; Anemia, Iron-Deficiency; Dementia; Cognitive Dysfunction; Cerebral Infarction; Dementia, Vascular; Hematinics; Ferrous succinate
• Other Study ID Numbers: 2018YFC1312303

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No