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

• Sponsor: Jon Unosson (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05744219
• Collaborator: (none)
• Enrollment: 338
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 56
• Patients Per Site Per Month: 6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Surgery; Liver Metastases; Liver Cancer; Pancreas Cancer; Aortic Aneurysm	Drug: Ferric carboxymaltose; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 338 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: At end of surgery, peri-operative blood loss is determined and if 400-4000 ml, the patient is randomised to iv Ferric Carboxymaltose 1000 mg or placebo.At end of surgery, peri-operative blood loss is determined and if 400-4000 ml, the patient is randomised to iv Ferric Carboxymaltose 1000 mg or placebo.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The attending nurse at the postoperative ward will do the final preparation of study drug and thus be aware of which patient receives placebo or iv iron. As the Ferric Carboxymaltose solution is opaque, the study drug is kept concealed behind the patient. Most patients have amnesia of the first hours after general anaesthesia. This effect is more pronounced after long and complex surgery which is the case for all patients included in this trial. Blinding from the patent's perspective is therefore not expected to be a major concern. The personnel preparing the study drug and nurse at the postoperative ward does not participate in care beyond this point, ensuring blinding is maintained.
• Primary Purpose: Treatment
• Official Title: Improved Recovery by Iron Following Surgery With Blood Loss, a Double-blind Multi-centre Randomized Controlled Phase III Drug Trial (the IRIS-trial)
• Anticipated Study Start Date: Aug 1, 2023
• Anticipated Primary Completion Date: Dec 31, 2027
• Anticipated Study Completion Date: Mar 30, 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Recovery after iv Iron [Five weeks]

   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)

Secondary Outcome Measures

1. Hb [One to five weeks]

   Assess if effects of the intervention are linked to increased post operative Hb (g/L)

2. Complications [One to five weeks]

   To assess if the intervention reduce post operative complications measured by the comprehensive complication index

3. Recovery [One to five weeks]

   To assess if the intervention affect recovery measured by the post operative morbidity survey

4. Performance status [Five weeks]

   To assess if the intervention affect performance assessed by Karnofsky performance status

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Uppsala University Hospital	Uppsala	Sverige	Sweden

Sponsors and Collaborators

• Jon Unosson

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jon Unosson, Principal Investigator, Uppsala University Hospital
• ClinicalTrials.gov Identifier: NCT05744219
• Other Study ID Numbers: IRIS
• First Posted: Feb 24, 2023
• Last Update Posted: Feb 24, 2023
• Last Verified: Feb 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Pancreatic Neoplasms; Aneurysm; Aortic Aneurysm

Study Results

No Results Posted as of Feb 24, 2023