search
Back to results

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

Primary Purpose

Surgery, Liver Metastases, Liver Cancer

Status
Not yet recruiting
Phase
Phase 3
Locations
Sweden
Study Type
Interventional
Intervention
Ferric carboxymaltose
Placebo
Sponsored by
Jon Unosson
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Surgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Provision of written informed consent Male and female patients Weight > 50 kg > 18 years of age Scheduled for complex aortic surgery, liver resection or pancreatic resection Exclusion Criteria: Short expected survival (less than six months) Intra-venous iron therapy within one month prior to surgery Severe anaemia (B-Hb <80 mg/L) prior to surgery Contraindication to Ferric Carboxymaltose according to SmPC Iron overloading disorder, i.e. hemochromatosis Risk of small for size future liver remnant Pre-operative renal replacement therapy Enrolled in another drug or medical device study within 30 days prior to enrolment of the current study Another planned major surgical procedure before the five week follow up Unsuitable for inclusion according to the investigator Pregnancy

Sites / Locations

  • Uppsala University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Iv Iron

Placebo

Arm Description

Ferric Carboxymaltose, single dose, Intra venous 1000 mg in 100 ml 0.9% NaCl

Placebo, single dose, Intra venous 0.9% NaCl 100 ml

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

Full Information

First Posted
February 6, 2023
Last Updated
February 15, 2023
Sponsor
Jon Unosson
search

1. Study Identification

Unique Protocol Identification Number
NCT05744219
Brief Title
Improved Recovery by Iron Following Surgery With Blood Loss, the IRIS-trial
Acronym
IRIS
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 1, 2023 (Anticipated)
Primary Completion Date
December 31, 2027 (Anticipated)
Study Completion Date
March 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jon Unosson

4. Oversight

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
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Surgery, Liver Metastases, Liver Cancer, Pancreas Cancer, Aortic Aneurysm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
338 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Iv Iron
Arm Type
Experimental
Arm Description
Ferric Carboxymaltose, single dose, Intra venous 1000 mg in 100 ml 0.9% NaCl
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, single dose, Intra venous 0.9% NaCl 100 ml
Intervention Type
Drug
Intervention Name(s)
Ferric carboxymaltose
Intervention Description
Active drug
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Recovery after iv Iron
Description
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)
Time Frame
Five weeks
Secondary Outcome Measure Information:
Title
Hb
Description
Assess if effects of the intervention are linked to increased post operative Hb (g/L)
Time Frame
One to five weeks
Title
Complications
Description
To assess if the intervention reduce post operative complications measured by the comprehensive complication index
Time Frame
One to five weeks
Title
Recovery
Description
To assess if the intervention affect recovery measured by the post operative morbidity survey
Time Frame
One to five weeks
Title
Performance status
Description
To assess if the intervention affect performance assessed by Karnofsky performance status
Time Frame
Five weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of written informed consent Male and female patients Weight > 50 kg > 18 years of age Scheduled for complex aortic surgery, liver resection or pancreatic resection Exclusion Criteria: Short expected survival (less than six months) Intra-venous iron therapy within one month prior to surgery Severe anaemia (B-Hb <80 mg/L) prior to surgery Contraindication to Ferric Carboxymaltose according to SmPC Iron overloading disorder, i.e. hemochromatosis Risk of small for size future liver remnant Pre-operative renal replacement therapy Enrolled in another drug or medical device study within 30 days prior to enrolment of the current study Another planned major surgical procedure before the five week follow up Unsuitable for inclusion according to the investigator Pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jon Unosson, MDPhD
Phone
+46186110000
Email
jon.unosson@surgsci.uu.se
Facility Information:
Facility Name
Uppsala University Hospital
City
Uppsala
State/Province
Sverige
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
May be available on request

Learn more about this trial

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

We'll reach out to this number within 24 hrs