Clinical trial NCT04083755: Impact of Intravenous Iron Treatment of Preoperative Anemia in Patients With LEAD (IRONPAD)
Official title: Impact of Intravenous Iron Treatment of Preoperative Anemia in Patients With Lower Extremity Peripheral Artery Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Anemia
Peripheral Arterial Occlusive Disease
Keywords: anemia
iron
surgery
PAD
Lead sponsor: Biocruces Bizkaia Health Research Institute
Sponsor class: OTHER_GOV
Collaborators: name: Sociedad Espanola de Angiologia y Cirugia Vascular
First posted: 2019-09-10
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Introduction: Anaemia due to iron and vitamin deficiency among patients with critical limb ischemia is high (\>50%). The prevalence of a higher rate of anaemia extends into the three months prior to revascularization surgery, it is associated with longer hospital stays and more transfusions in addition to being a factor in poor prognoses. Study and treatment of anaemia within the perioperative period could improve the surgical outcomes, including the recovery and the quality of patients' lives. There are several types of intravenous iron preparations with different administration protocols, but there is not a consensus on the timing and type of the appropriate iron therapy. To the best of our knowledge, there is no data on the performance of intravenous iron in the management of preoperative anaemia in patients with peripheral artery disease (PAD) in vascular surgery.

Methods and analysis: The IRONPAD Study is a phase IV randomised controlled trial with two branches of treatment on the efficacy of intravenous iron therapy for the optimisation of blood use and prognosis in the perioperative period of patients with anaemia undergoing revascularisation for chronic lower limb ischemia. The study randomises 240 patients with anaemia to: treat with a single intravenous dose of ferric carboxymaltose (1000 mg) or no treatment vs oral iron supplements (if severe anaemia) a minimum of two days prior to lower limb revascularisation surgery. The primary outcome is to reduce the incidence of transfusion from randomisation up to 30+7 days after the main surgery. The secondary outcomes will be included to establish the optimal preoperative moment of increased intravenous iron administration, to raise haemoglobin levels; to study the evolution of haemoglobin from inclusion to 30+7 days after surgery; and to determine the impact of anaemia and its treatment on the length of hospital stay, morbidity and mortality, as well as the quality of life in this period.

Detailed description: The IRONPAD Study is a phase IV randomised controlled trial with two branches of treatment on the efficacy of intravenous iron therapy for the optimisation of blood use and prognosis in the perioperative period of patients with anaemia undergoing revascularisation for chronic lower limb ischemia.

Patients admitted to hospital with anaemia and indication of elective revascularisation surgery for chronic ischemia of the lower limbs will be eligible for screening. Anaemia in this study is established following the WHO criteria with haemoglobin (Hb) \<130 g/L in men and \<120 g/L in women 21.

Patients will be selected according to the usual practice, without excluding patients because of comorbidity or other reasons that may affect results (selection bias).

Prior to inclusion, freely given written informed consent will be obtained from all patients. Once included, each patient will be masked into a unique identity number (correlative according to inclusion), as a reference of patient ID in the registry.

Each patient will be randomised to a line A or line B of treatment.

* Line A: a single, ferric carboxymaltose (Ferinject®) 1000 mg IV iron dose administration. The infusion will be according to product specifications with an approximate duration of 15 minutes during hospitalisation and will not require an additional site visit or extended period of hospitalisation.
* Line B: control. The control group will not receive specific treatment. In case of severe iron deficiency anaemia, oral iron supplements (iron sulphate dihydrate) will be given.

Both lines may be followed in addition to taking vitamin B12 and folic acid, if indicated.

The patient, once included in the study, may receive a blood transfusion if the following criteria are met:

- Absolute indication: Hemodynamic instability Active bleeding Hb \<7 g/dl

- Relative indications: in case of Hb \<8.5 g/dL or haematocrit \<28% following the clinical criteria of the medical specialist.

Interventions to be measured:

The data collected at baseline will include patients' past medical history, medications, blood tests (including hemogram, iron tests and renal function), comorbidity index (Charlson Scale), lower limbs chronic ischemia category and the limb scheduled for revascularisation (including registry of any trophic lesions and if they have signs of active infection), height, weight and body-mass index of the patient. In addition, already validated quality of life questionnaire, the Short Form-36 Health Survey (SF-36) will be completed.

Procedure data will record: date of IV iron treatment, if received, dose and any adverse events during or after administration; ASA (American Society of Anaesthesiologists) risk level; type of surgery performed for revascularisation of lower limbs, information on clinical success and complications of the intervention. Blood records will include haemoglobin before and first day after surgery and number of red blood cell units of or any other blood component transfused during the surgical procedure. If surgery does not finally take place, data from the 30 days after inclusion will be registered for analysis with intention to treat.

The hospital discharge visit will record: date of discharge; last hemogram; number of blood transfusions from the postoperative period until discharge; days in intensive care; adverse events such as medical and surgical complications as well as mortality.

The final follow-up visit will take place 30 days after the main surgery (with + 7 day window) it would be performed by telephone, in the outpatient consultation or in the hospital if the patient continues to be hospitalised; in that case, the discharge visit and final visit will be made simultaneously. It will record: blood tests (including hemogram, iron tests), clinical success, serious adverse events (SAE) and mortality, which may have occurred between hospital discharge and the visit in addition to Short Form-36 Health Survey (SF-36). See Fig. 1 for Assessment flow diagram.

Eligibility criteria: Inclusion Criteria:

* Patients of both sexes over 18 years
* Patients diagnosed with anemia, considered as Hb \<13.0 g/dL in mens and Hb\<12g/dL in women
* Patients diagnosed with symptomatic chronic lower limb ischemia (degrees 2-5 by Rutherford-Baker, both included, Fontaine II-IV), who will undergo surgical revascularization (endovascular or open) and accept treatment
* Revascularization surgery scheduled in the approximate minimum period of two days, (\> 48 hours) from the inclusion, Patients diagnosed with iron deficiency anemia being treated with oral iron in their usual medication and with inadequate iron storage for surgical intervention (ferritin \<100 ng/ml) or functional iron deficiency: ferritin 100-500 ng/ml with TSI \< 20% .
* They are able and willing to give written informed consent at the time of selection

Exclusion Criteria:

* Patients with acute ischemia will be excluded
* Severe anemia \< 8 gr/dL
* Arterial hypertension not controlled with antihypertensive medication (considered with systolic blood pressure\> 180mmHg or diastolic\> 100mmHg)
* Acute renal failure or renal failure with creatinine clearance \<30mmHg
* Patient with documented intolerance or allergy to iron or its derivatives
* Unstable angina, defined as electrocardiographic changes with chest pain that indicate resting myocardial ischemia
* History of stroke in the previous 6 months
* Patients with thrombocytopenia less than 50,000ug/dl or alterations in coagulation
* That you are simultaneously participating in a clinical trial that conditions or modifies the registry
* Pregnancy or lactation (pregnancy tests in women of childbearing age according to usual practice)
* Rejection of treatment or inclusion in the registry by the patient
* Patients who refuse to receive transfusions of blood products (for example, Jehovah's Witnesses)
* Patients with criteria of SEPSIS
* Patients with Ferritin \<30 ng/ml that will be directed for digestive study
* Patients with active neoplasia
* Probable or confirmed case with active SARS-CoV-2 infection
* Patients who are not able to give their informed consent or understand the study procedure

Primary outcomes:
measure: To reduce the incidence of transfusion (receiving any volume of 1 unit or more than 1 unit of packed red cells) from randomisation up to 30 days (with +/- 15-day window) after the main surgery
timeFrame: From inclusion date to 30 days (with +7 window) after the main surgery
Secondary outcomes:
measure: Changes and evolution of hemoglobin during admission; difference in hemoglobin (Hb) between inclusion, intervention and discharge.
timeFrame: From inclusion date to 30 days (with +7day window) after surgical procedure
measure: Establish the optimal preoperative moment of increased intravenous iron yield to increase Hb
timeFrame: From inclusion date to 30 days (with +7 window) after the main surgery
measure: Impact of anemia and its treatment on the length of hospital stay
timeFrame: From inclusion date to 30 days (with +7 window) after the main surgery
measure: Impact of anemia and its treatment on morbidity
timeFrame: From inclusion date to 30 days (with +7 window) after the main surgery
measure: Impact of anemia and its treatment on mortality
timeFrame: From inclusion date to 30 days (with +7 window) after the main surgery
measure: Impact of anemia and its treatment on quality of life
timeFrame: From inclusion date to 30 days (with +7 window) after the main surgery
Other outcomes:
Locations:
city: Galdakao
country: Spain
facility: Hospital de Galdakao-Usansolo.
state: Basque Country
city: Baracaldo
country: Spain
facility: Servicio de Angiología y Cirugía vascular del Hospital Universitario Cruces
state: Biscay
city: Getafe
country: Spain
facility: Hospital de Getafe
state: Madrid
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Vascular Surgeon
name: Ana Apodaka Diez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Internal Medicine
name: Jose Manuel Rodriguez Chinesta, MD
role: PRINCIPAL_INVESTIGATOR
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