Phase III IV Iron Trial for Anaemia in Major Surgery (PREVENTT)

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| Summary | |
| --- | |
| EudraCT Number: | 2012-002786-35 |
| Sponsor's Protocol Code Number: | 12/0246 |
| National Competent Authority: | UK - MHRA |
| Clinical Trial Type: | EEA CTA |
| Trial Status: | Completed |
| Date on which this record was first entered in the EudraCT database: | 2012-09-07 |
| Trial results | View results |

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| A. Protocol Information

| B. Sponsor Information

| D. IMP Identification

| D.8 Information on Placebo

| E. General Information on the Trial

To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on post-operative morbidity, length of hospital stay and mortality.

To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on health related quality of life.

To evaluate resource use and costs associated with the treatment with intravenous ferric carboxymaltose (Ferinject®) compared with placebo.

To evaluate the tolerability and safety of Ferinject® compared with placebo from randomisation till study termination.

To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on:
o Complications of the intervention itself.
o Complications from blood transfusion or blood products. | | To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on change in haemoglobin levels.

To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on post-operative morbidity, length of hospital stay and mortality.

To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on health related quality of life.

To evaluate resource use and costs associated with the treatment with intravenous ferric carboxymaltose (Ferinject®) compared with placebo.

To evaluate the tolerability and safety of Ferinject® compared with placebo from randomisation till study termination.

To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on:
o Complications of the intervention itself.
o Complications from blood transfusion or blood products. |
| To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on change in haemoglobin levels.

To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on post-operative morbidity, length of hospital stay and mortality.

To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on health related quality of life.

To evaluate resource use and costs associated with the treatment with intravenous ferric carboxymaltose (Ferinject®) compared with placebo.

To evaluate the tolerability and safety of Ferinject® compared with placebo from randomisation till study termination.

To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on:
o Complications of the intervention itself.
o Complications from blood transfusion or blood products. |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | | 1. At least 18 years of age and signed written informed consent.
2. Patients undergoing elective major open abdominal surgery.
a. The Indication for operation may be for benign or malignant disease.
b. Major Surgery is defined as an operation of anticipated duration more than one hour.
3. Screening haemoglobin (Hb) greater than or equal to 90 g/L (9.0 g/dL) but below or equal to 120 g/L (12.0 g/dL) in women or 130g/L (13.0g.dL) in men within four weeks of randomisation.
4. Randomisation and administration of study infusion a minimum of 10 days and maximum 42 days before planned operation.
5. Negative pregnancy test for women of childbearing potential (within last 7 days), and agree to use effective form of contraception until 6 weeks post treatment.
6. Laboratory data used for determination of eligibility at the baseline visit must not be older than four weeks. | | 1. At least 18 years of age and signed written informed consent.
2. Patients undergoing elective major open abdominal surgery.
a. The Indication for operation may be for benign or malignant disease.
b. Major Surgery is defined as an operation of anticipated duration more than one hour.
3. Screening haemoglobin (Hb) greater than or equal to 90 g/L (9.0 g/dL) but below or equal to 120 g/L (12.0 g/dL) in women or 130g/L (13.0g.dL) in men within four weeks of randomisation.
4. Randomisation and administration of study infusion a minimum of 10 days and maximum 42 days before planned operation.
5. Negative pregnancy test for women of childbearing potential (within last 7 days), and agree to use effective form of contraception until 6 weeks post treatment.
6. Laboratory data used for determination of eligibility at the baseline visit must not be older than four weeks. |
| 1. At least 18 years of age and signed written informed consent.
2. Patients undergoing elective major open abdominal surgery.
a. The Indication for operation may be for benign or malignant disease.
b. Major Surgery is defined as an operation of anticipated duration more than one hour.
3. Screening haemoglobin (Hb) greater than or equal to 90 g/L (9.0 g/dL) but below or equal to 120 g/L (12.0 g/dL) in women or 130g/L (13.0g.dL) in men within four weeks of randomisation.
4. Randomisation and administration of study infusion a minimum of 10 days and maximum 42 days before planned operation.
5. Negative pregnancy test for women of childbearing potential (within last 7 days), and agree to use effective form of contraception until 6 weeks post treatment.
6. Laboratory data used for determination of eligibility at the baseline visit must not be older than four weeks. |
| E.4 | Principal exclusion criteria | | 1. Patients undergoing laparoscopic surgery.
2. Body weight under 50kg.
3. Known history of acquired iron overload, or family history of haemochromatosis or thalassemia or TSAT >50%.
4. Known reason for anaemia (e.g. untreated B12 or folate deficiency or haemoglobinopathy).
5. Known hypersensitivity to ferric carboxymaltose (Ferinject®) or its excipients.
6. Temperature > 37.5C or patient on non-prophylactic antibiotics
7. Known chronic liver disease
8. If clinically indicated for the patient to have LFT’s as part of preassessment for surgery and this screening alanine transaminase (ALT) or aspartate transaminase (AST) is above three times the upper limit of the normal range.
9. Received erythropoietin or i.v. iron therapy in the previous 12 weeks.
10. Immunosuppressive therapy (for organ transplantation) or renal dialysis (current or planned within the next 12 months).
11. Patients with severe asthma or severe allergy (requiring hospitalisation within the last 12 months).
12. Unfit for elective surgery.
13. Pregnancy or lactation.
14. Inability to fully comprehend and/or perform study procedures in the investigator’s opinion.
15. Patient involvement in another IMP trial within the previous 4 weeks, prior to randomisation. Involvement in another IMP trial, following randomisation, that may impact on the results of the PREVENTT trial. | | 1. Patients undergoing laparoscopic surgery.
2. Body weight under 50kg.
3. Known history of acquired iron overload, or family history of haemochromatosis or thalassemia or TSAT >50%.
4. Known reason for anaemia (e.g. untreated B12 or folate deficiency or haemoglobinopathy).
5. Known hypersensitivity to ferric carboxymaltose (Ferinject®) or its excipients.
6. Temperature > 37.5C or patient on non-prophylactic antibiotics
7. Known chronic liver disease
8. If clinically indicated for the patient to have LFT’s as part of preassessment for surgery and this screening alanine transaminase (ALT) or aspartate transaminase (AST) is above three times the upper limit of the normal range.
9. Received erythropoietin or i.v. iron therapy in the previous 12 weeks.
10. Immunosuppressive therapy (for organ transplantation) or renal dialysis (current or planned within the next 12 months).
11. Patients with severe asthma or severe allergy (requiring hospitalisation within the last 12 months).
12. Unfit for elective surgery.
13. Pregnancy or lactation.
14. Inability to fully comprehend and/or perform study procedures in the investigator’s opinion.
15. Patient involvement in another IMP trial within the previous 4 weeks, prior to randomisation. Involvement in another IMP trial, following randomisation, that may impact on the results of the PREVENTT trial. |
| 1. Patients undergoing laparoscopic surgery.
2. Body weight under 50kg.
3. Known history of acquired iron overload, or family history of haemochromatosis or thalassemia or TSAT >50%.
4. Known reason for anaemia (e.g. untreated B12 or folate deficiency or haemoglobinopathy).
5. Known hypersensitivity to ferric carboxymaltose (Ferinject®) or its excipients.
6. Temperature > 37.5C or patient on non-prophylactic antibiotics
7. Known chronic liver disease
8. If clinically indicated for the patient to have LFT’s as part of preassessment for surgery and this screening alanine transaminase (ALT) or aspartate transaminase (AST) is above three times the upper limit of the normal range.
9. Received erythropoietin or i.v. iron therapy in the previous 12 weeks.
10. Immunosuppressive therapy (for organ transplantation) or renal dialysis (current or planned within the next 12 months).
11. Patients with severe asthma or severe allergy (requiring hospitalisation within the last 12 months).
12. Unfit for elective surgery.
13. Pregnancy or lactation.
14. Inability to fully comprehend and/or perform study procedures in the investigator’s opinion.
15. Patient involvement in another IMP trial within the previous 4 weeks, prior to randomisation. Involvement in another IMP trial, following randomisation, that may impact on the results of the PREVENTT trial. |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The co-primary outcomes are:
• Risk of blood transfusion or death from randomisation until 30-days following the index operation.
• Blood transfusion rate (including repeat transfusions) from randomisation until 30-days following the index operation. | | The co-primary outcomes are:
• Risk of blood transfusion or death from randomisation until 30-days following the index operation.
• Blood transfusion rate (including repeat transfusions) from randomisation until 30-days following the index operation. |
| The co-primary outcomes are:
• Risk of blood transfusion or death from randomisation until 30-days following the index operation.
• Blood transfusion rate (including repeat transfusions) from randomisation until 30-days following the index operation. |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | 30-days post operation | | 30-days post operation |
| 30-days post operation |
| E.5.2 | Secondary end point(s) | | Change in haemoglobin levels; total number of units of blood transfused; post operative morbidity; change in health related quality of life (HRQOL); health economic outcome; safety & related efficacy outcomes. | | Change in haemoglobin levels; total number of units of blood transfused; post operative morbidity; change in health related quality of life (HRQOL); health economic outcome; safety & related efficacy outcomes. |
| Change in haemoglobin levels; total number of units of blood transfused; post operative morbidity; change in health related quality of life (HRQOL); health economic outcome; safety & related efficacy outcomes. |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | | Change in haemoglobin levels – at operation and 8 weeks and 6 months post operation;
Total number of units of blood transfused – at 30 days post operation;
Post operative morbidity – at 3 days, 5 days, 7 days and 14 days post operation;
Change in HRQOL from baseline to – 10 days post transfusion, 8 weeks and 6 months post operation. | | Change in haemoglobin levels – at operation and 8 weeks and 6 months post operation;
Total number of units of blood transfused – at 30 days post operation;
Post operative morbidity – at 3 days, 5 days, 7 days and 14 days post operation;
Change in HRQOL from baseline to – 10 days post transfusion, 8 weeks and 6 months post operation. |
| Change in haemoglobin levels – at operation and 8 weeks and 6 months post operation;
Total number of units of blood transfused – at 30 days post operation;
Post operative morbidity – at 3 days, 5 days, 7 days and 14 days post operation;
Change in HRQOL from baseline to – 10 days post transfusion, 8 weeks and 6 months post operation. |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 35 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 | Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial | | LVLS | | LVLS |
| LVLS |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 31 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 31 |

| F. Population of Trial Subjects

| G. Investigator Networks to be involved in the Trial

| N. Review by the Competent Authority or Ethics Committee in the country concerned

| P. End of Trial