Improved Recovery by Iron Following Surgery With Blood Loss, the IRIS-trial (IRIS)

Improved Recovery by Iron Following Surgery With Blood Loss, a Double-blind Multi-centre Randomized Controlled Phase III Drug Trial (the IRIS-trial)

The aim of the study is to investigate if iv iron formulation improve recovery after surgery with blood loss.

Post-operative anaemia is a common debilitating condition after major surgery due to a combination of preoperative iron deficiency anaemia (IDA) and per-operative blood loss. Median blood loss following hepatopancreatobiliary (HPB) and complex aortic surgery typically range between 500-1000 ml. Bioavailability of iron may be a rate limiting factor in erythropoiesis in anaemia secondary to blood loss. For the IRIS trial, it is hypothesized that intravenously (iv) administered Ferric Carboxymaltose after a per-operative blood loss of 400-4000 ml, improves post-operative recovery and reduces the RBC transfusion.

Patients scheduled for elective HPB surgery or complex aortic surgery will be screened for eligibility and recruited into the study.

By the end of the surgical procedure, if blood loss is estimated to 400-4000 ml, the patient is randomized 1:1 to iv 1000 mg Ferric Carboxymaltose or placebo.

The primary endpoint is a composite of death, number of RBC transfusions, post-operative severe anemia (Hb <80 g/L) and FACT-An Quality of life (QoL) five weeks after surgery, assessed by win ratio.

The trial will also examine effects on; a) levels of Hb; b) markers of erythropoiesis and iron bioavailability; c) post-operative complications; d) post-operative recovery; e) performance status; f) subgroups based on type of surgery and degree of anemia and iron deficiency; g) re-admissions; h) long term outcome based on patient medical records and i) how post-operative recovery differs between those with low (<400 ml), high (400-4000 ml) and very high (>4000 ml) per-operative blood loss.

Recruitment will continue until 338 patients are randomized or 304 have completed the five week follow up

The coordinating center of the trial is the Department of Surgery at Uppsala University Hospital. Participating sites are also Linköping University Hospital and Lund University Hospital, all in Sweden. Other sites may be added.

Study Overview

• Status: Not yet recruiting
• Conditions: Surgery; Liver Metastases; Pancreas Cancer; Aortic Aneurysm; Liver Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Ferric carboxymaltose

• Study Type: Interventional
• Enrollment (Anticipated): 338
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jon Unosson, MDPhD; Phone Number: +46186110000; Email: jon.unosson@surgsci.uu.se

Study Locations

• Sweden
  • Sverige
    • Uppsala, Sverige, Sweden
      • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of written informed consent
2. Male and female patients
3. Weight > 50 kg
4. > 18 years of age
5. Scheduled for complex aortic surgery, liver resection or pancreatic resection

Exclusion Criteria:

1. Short expected survival (less than six months)
2. Intra-venous iron therapy within one month prior to surgery
3. Severe anaemia (B-Hb <80 mg/L) prior to surgery
4. Contraindication to Ferric Carboxymaltose according to SmPC
5. Iron overloading disorder, i.e. hemochromatosis
6. Risk of small for size future liver remnant
7. Pre-operative renal replacement therapy
8. Enrolled in another drug or medical device study within 30 days prior to enrolment of the current study
9. Another planned major surgical procedure before the five week follow up
10. Unsuitable for inclusion according to the investigator
11. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iv Iron; Ferric Carboxymaltose, single dose, Intra venous 1000 mg in 100 ml 0.9% NaCl	Drug: Ferric carboxymaltose; Active drug
Placebo Comparator: Placebo; Placebo, single dose, Intra venous 0.9% NaCl 100 ml	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery after iv Iron	To examine if 1000 mg iv Ferric Carboxymaltose administered immediately following hepatic or pancreatic resection or complex aortic surgery with 400 - 4000 ml perioperative blood loss affect a composite of death, number of RBC transfusions, prevalence of post-operative severe anaemia (Hb < 80 g/L) and change in FACT-An QoL questionnaire score at five weeks after surgery compared to pre-operative baseline score. The composite endpoint is assessed by win ratio in the following order: Alive at five weeks (yes/no); number of RBC transfusions from surgery until five weeks; severe anaemia with Hb <80 g/L any time after surgery until five weeks (yes/no); FACT-An score (score at five weeks minus score at baseline)	Five weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hb	Assess if effects of the intervention are linked to increased post operative Hb (g/L)	One to five weeks
Complications	To assess if the intervention reduce post operative complications measured by the comprehensive complication index	One to five weeks
Recovery	To assess if the intervention affect recovery measured by the post operative morbidity survey	One to five weeks
Performance status	To assess if the intervention affect performance assessed by Karnofsky performance status	Five weeks

Collaborators and Investigators

• Sponsor: Jon Unosson

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2023
• Primary Completion (Anticipated): December 31, 2027
• Study Completion (Anticipated): March 30, 2028

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Actual): February 24, 2023

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Aortic Diseases; Pancreatic Neoplasms; Aneurysm; Aortic Aneurysm
• Other Study ID Numbers: IRIS (Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: May be available on request

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