E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-anemic Patients Undergoing Elective or Sub-Acute CABG, Valve Replacement or a Combination thereof |
Non-anæmiske Patienter, der får foretaget elektiv eller subakut CABG, hjerteklapudskiftning eller en kombination heraf |
|
E.1.1.1 | Medical condition in easily understood language |
Non-anemic Patients undergoing planned or sub-acute heart bypass surgery (CABG), heart valve replacement or a combination thereof. |
Non-anæmiske Patienter der får foretaget planlagt eller sub-akut hjerte bypassoperation (CABG), hjerteklap udskiftning eller en kombination heraf.
|
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054312 |
E.1.2 | Term | Anemia postoperative |
E.1.2 | System Organ Class | 100000004863 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that intravenous iron isomaltoside 1000 (Monofer®) is superior compared to placebo in leading to a less decrease in the haemoglobin level in non-anemic patients undergoing cardiac surgery |
At påvise superioritet af intravenøst jernisomaltosid 1000 (Monofer®) i forhold til placebo i forhold til at nedsætte et fald i hæmoglobinindholdet hos non-anæmiske patienter, der får foretaget hjerteoperationer |
|
E.2.2 | Secondary objectives of the trial |
• The secondary purpose of the study is to compare the effect of jernisomaltosid 1000 and placebo on:
Need for blood transfusion
Iron Related Parameters
Time of Hospitalization
Functional capabilities
Safety |
• De sekundære formål i studiet er at sammenligne effekten af jernisomaltosid 1000 og placebo på:
Behov for blodtransfusion
Jernrelaterede parametre
Indlæggelsestid
Funktionel formåen
Sikkerhed |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be suitable for inclusion in the study, the subjects meet the following criteria:
1. Men and women over 18 years.
2. Non-anemic Patients undergoing elective or subacute CABG, heart valve replacement or a combination thereof.
3. Women: Hb ≥ 12.0 g / dl (7.45 mmol / l), men: Hb ≥ 13.0 g / dl (8.1 mmol / l).
4. Willingness to participate after informed consent. |
For at være egnet til inklusion i forsøget skal forsøgspersonerne opfylde følgende kriterier:
1. Mænd og kvinder over 18 år.
2. Non-anæmiske Patienter, der får foretaget elektiv eller subakut CABG, hjerteklapudskiftning eller en kombination heraf.
3. Kvinder: Hb ≥ 12.0 g/dl (7,45 mmol/l), mænd: Hb ≥ 13,0 g/dl (8,1 mmol/l).
4. Villighed til at deltage efter informeret samtykke. |
|
E.4 | Principal exclusion criteria |
Individuals who meet one or more of the following criteria are unsuitable for inclusion in the study:
1. Participants who have received blood transfusion within 30 days prior to screening, and / or during the elective CABG or subacute, heart valve replacement, or a combination thereof.
2. Iron Overload or disturbances in utilization of iron (eg. Haemochromatosis and haemosiderosis)
3. Serum ferritin> 800 ng / ml.
4. Known hypersensitivity to any of the excipients of the study drug.
5. Multiple allergies in medical history.
6. Decompensated cirrhosis and hepatitis.
7. Alanine aminotransferase (ALT)> 3 times upper limit of normal.
8. Acute infections (after clinical assessment).
9. Rheumatoid arthritis with symptoms or signs of active joint inflammation.
10. The patient is pregnant or breast-feeding. (To exclude pregnancy, women must be postmenopausal (at least 12 months since the last menstrual period) or sterilized or, for women of childbearing potential, use one of the following methods of contraception throughout the trial and for a period after termination representing at least 5 biological plasma half-lives of study drug: P contraceptives, intrauterine devices, parenteral contraception with depot effect (prolonged release formulation with progestin), subdermal implant, vaginal ring or transdermal patches).
11. Participation in another clinical trial, in a period prior to screening corresponding to less than 5 half-lives of the experimental drug.
12. Untreated Vitamin B12 or folate deficiency.
13. Another iv or oral iron therapy within 4 weeks prior to screening visit.
14. Erythropoietin treatment within 4 weeks prior to screening visit.
15. Impaired renal function defined by se-creatinine> 150μmol / l |
Personer, der opfylder et eller flere af følgende kriterier, er uegnede til inklusion i forsøget:
1. Deltagere som har modtaget blodtransfusion indenfor 30 dage før screening og/eller under den elektive eller subakutte CABG, hjerteklapudskiftning eller en kombination heraf.
2. Jernoverload eller forstyrrelser i jernudnyttelsen (f.eks. hæmokromatose og hæmosiderose)
3. Serumferritin >800 ng/ml.
4. Kendt overfølsomhed over for et eller flere af hjælpestofferne i forsøgslægemidlet.
5. Multiple allergier i anamnesen.
6. Dekompenseret levercirrhose og hepatitis.
7. Alaninaminotransferase (ALT) > 3 gange øvre normalgrænse.
8. Akutte infektioner (efter klinisk vurdering).
9. Rheumatoid arthritis med symptomer eller tegn på aktiv ledinflammation.
10. Patienten er gravid eller ammer. (For at udelukke graviditet skal kvinder være postmenopausale (mindst 12 måneder siden sidste menstruation) eller steriliseret eller, for fødedygtige kvinder, anvende en af følgende antikonceptionsmetoder i hele forsøgsperioden og i en periode efter forsøgets afslutning svarende til mindst 5 biologiske plasmahalveringstider af forsøgslægemidlet: P-piller, spiral, parenteral antikonception med depotvirkning (depotpræparat med gestagen), subdermalt implantat, vaginalring eller depotplastre).
11. Deltagelse i et andet klinisk forsøg i et tidsrum inden screeningen svarende til mindre end 5 halveringstider af det pågældende forsøgslægemiddel.
12. Ubehandlet vitamin B12- eller folatmangel.
13. Anden iv eller peroral jernbehandling inden for 4 uger før screeningsbesøget.
14. Behandling med erythropoietin inden for 4 uger før screeningsbesøget.
15. Påvirket nyrefunktion defineret ved se-creatinin > 150μmol/l |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The trial's primary endpoint is:
Changes in hemoglobin concentration from baseline (ie preoperatively - the day before surgery or surgery day) for 4 weeks postoperatively. |
Forsøgets primære endpoint er:
Ændring i hæmoglobinkoncentrationen fra baseline (dvs. præoperativt – dagen før operationen eller operationsdagen) til 4 uger postoperativt. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 weeks postoperatively |
4 uger postoperativt. |
|
E.5.2 | Secondary end point(s) |
The secondary end points of the study are:
• Proportion of patients that are anaemic (women < 12 g/dL and men < 13 g/dL) at day 5 and week 4
• Proportion of patients able to maintain Hb between 9.5 and 12.5 g/dL (both values included) at day 5 and week 4.
• Number of patients in each randomisation group who need blood transfusion and number of transfusions administered
• Change from baseline (preoperatively - the day before surgery or same day) in concentrations of serum ferritin, serum iron, TfS, and reticulocytes at day 5 and week 4
• Number of postoperative days to discharge
• Changes in New York Heart Association (NYHA) classification from baseline to 4 weeks post operatively
• Number of patients in each randomisation group who experience any study drug related adverse events (AEs/SAEs/SUSARs)
|
Forsøgets sekundære endpoints er:
• andel patienter, der er anæmisk (kvinder < 12 g/dL og mænd <13 g/dL) på dag 5 og uge 4
• andel patienter i stand til at opretholde Hb mellem 9,5 og 12,5 g/dL (begge værdier inkluderet) på dag 5 og uge 4.
• antal transfusionskrævende patienter og antal foretagne transfusioner i hver randomiseringsgruppe
• ændring i koncentrationen af serumferritin, serumjern (TfS) og reticulocytter fra baseline (dvs. præoperativt – dagen før operationen eller operationsdagen) til dag 5 og uge 4
• antal dage postoperativt til udskrivning
• ændring i New York Heart Association (NYHA) klassificering fra baseline til 4 uger postoperativt
• antal patienter i hver randomiseringsgruppe, som kommer ud for forsøgsmedicinrelaterede uønskede hændelser (AE/SAE/SUSAR)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
4 weeks postoperatively |
4 uger postoperativt. |
|
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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |