Infusing Needed Iron to Target Insufficiency in Adults Treated for Evidence of Heart Failure (INITIATE-HF)

Kaiser Permanente

Status: Not yet enrolling

Conditions: Heart Failure and Mildly Reduced Ejection Fraction; Iron Deficiency (ID); Heart Failure and Reduced Ejection Fraction; Heart Failure

Treatments: Other: No Notification Group; Other: Notification Group

Study type: Interventional

Funder types: Other

Identifiers

NCT07467668

2090665

Details and patient eligibility

About

The INITIATE-HF study is a cluster randomized controlled trial that aims to find out if reminding doctors about treatment guidelines for iron deficiency in adults with heart failure who are hospitalized and have evidence of iron deficiency changes the subsequent use of intravenous (IV) iron.

Two groups of hospitalized adult patients with known heart failure and iron deficiency will be compared:

• Group 1 will include doctors who receive a notification with their patient's iron storage test results and guideline recommendations related to the use of IV iron.
• Group 2 will include doctors who do not receive this notification and continue with usual standard of care.

The study will measure if this provider-facing notification affects physician use of recommended IV iron treatment in eligible patients with heart failure, left ventricular ejection fraction less than 50%, and iron deficiency. Secondarily, if there is an increased use of IV iron observed in the intervention group, this study will evaluate whether there are differential health outcomes (i.e., fewer subsequent hospital visits and lower risk of death) of patients whose providers were assigned to the intervention group.

Full description

The INITIATE-HF study will be managed at the Kaiser Permanente Northern California (KPNC) Division of Research and will include participants from KPNC medical centers. Up to 21 medical centers will be randomly assigned into two groups, with balanced populations between the groups based on demographic and heart failure-related characteristics. In medical centers assigned to the intervention group, physicians of eligible patients with heart failure and iron deficiency (i.e., TSAT <20%) will be sent information from current KPNC and national clinical practice guidelines about the use of IV iron therapy in the setting of heart failure. In medical centers assigned to the control group, physicians will not be contacted about their patients with iron deficiency or receive information about current guidelines about the use of IV iron (i.e., usual care). If a patient with heart failure is admitted to a medical center assigned to the intervention group and has iron deficiency, their treating doctor will be notified about their patient's iron stores lab results, information from KPNC and national guidelines about the use of IV iron therapy, and details about the available IV iron formulations and recommended dosages for their consideration. The study team will not have any direct contact with patients at any of the medical centers assigned to either the intervention or control group and will not be involved in any clinical care decision-making for any patients, as that will reside with each patient's responsible physician and care team.

The intention-to-treat (ITT) population will consist of patients meeting all eligibility criteria at both intervention and control sites. The per-protocol population will include data from all patients at intervention sites. All primary and secondary endpoints will be analyzed using mixed effects Cox proportional hazards regression for point and interval estimation of the intervention effect on the primary outcome and on each of the secondary outcomes. Similarly, mixed effects Poisson regression will be additionally performed to analyze the effect of the intervention in relation to secondary outcomes when characterized as counts: all-cause and heart failure-specific outpatient encounters (i.e., clinic and telehealth visits), emergency department visits, and hospitalizations.

Interaction analyses will be performed to assess for potential heterogeneity of treatment effects based on the following prespecified subgroups: age, sex, race/ethnicity, presumed etiology of heart failure (i.e., ischemic vs. non-ischemic), duration of diagnosed heart failure (i.e., <1 vs. >1 year), reason for hospital admission (i.e., primary vs. secondary discharge diagnosis for heart failure), left ventricular ejection fraction category (<40% vs. 41-49%), B-type natriuretic peptide (BNP) level (i.e., < vs. > the median value), TSAT (i.e., <15% vs. 15-19%), estimated glomerular filtration rate (eGFR) level (i.e., < vs. > the median), hemoglobin level (i.e., < vs. > the median), anemia status, and KPNC service area.

The primary analysis will focus on the implementation outcome of the administration of IV iron during the index hospitalization to determine how the provider-facing notification influences provider behavior and care processes. The secondary analysis will evaluate effectiveness outcomes, including the composite of all-cause death and heart failure-related hospitalization, to determine whether any observed changes in the implementation process outcome also translate into improved patient clinical outcomes during the 12 months after randomization.

Enrollment: 3,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Adults (age >18 years); Diagnosed heart failure with most recent left ventricular ejection fraction <50%; Hospitalized for any reason for the index admission; Documented iron deficiency defined as TSAT <20% during the index hospitalization; At least 6 months of health plan coverage and prescription drug benefit before admission

Exclusion criteria

A documented allergy to IV iron in the Kaiser Permanente Northern California (KPNC) electronic health record (EHR) system; A history of hemochromatosis (i.e., iron overload) based on KPNC EHR data; End-stage kidney disease (defined as receiving chronic dialysis or a prior kidney transplant) or advanced chronic kidney disease (i.e., estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) based on most recent pre-admission outpatient laboratory results or the KPNC regional End-Stage Kidney Disease Treatment Registry; Serum ferritin >300 ng/mL based on KPNC EHR data; Diagnosed with metastatic cancer and/or receiving systemic chemotherapy based on KPNC EHR data; Institutionalized (e.g., prison) and/or receiving palliative care per KPNC EHR data

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

3,000 participants in 2 patient groups

Intervention Medical Center - Notification Group

Active Comparator group

Description:

In medical centers assigned to the intervention group, physicians of eligible patients will be sent a one-time notification with information about their patient's iron deficiency, current KPNC and national clinical practice guidelines about IV iron therapy, and available IV iron formulations and recommended dosages.

Treatment:

Other: Notification Group

Control Medical Center - No Notification Group

Active Comparator group

Description:

In medical centers assigned to the control group, physicians of eligible patients will NOT be sent information about their patients or current KPNC and national clinical practice guidelines about the use of IV iron therapy in the setting of heart failure.

Treatment:

Other: No Notification Group