E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe postpartum anaemia |
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E.1.1.1 | Medical condition in easily understood language |
Severe postpartum anaemia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036417 |
E.1.2 | Term | Postpartum haemorrhage |
E.1.2 | System Organ Class | 10036585 - Pregnancy, puerperium and perinatal conditions |
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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 |
The primary objective of this study is to get explorative information about IV high single dose infusion of iron isomaltoside 1000 compared to RBC transfusion in the treatment of severe PP-IDA evaluated as physical fatigue. |
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E.2.2 | Secondary objectives of the trial |
The secondary efficacy objectives of the study are to evaluate the effect of iron isomaltoside 1000 compared to RBC transfusion on
• Ability to increase Hb
• Other relevant iron and RBC related biochemical parameters
• Other fatigue symptoms
• Symptoms of postpartum depression.
• Time of postpartum lactogenesis
• Time of discontinuation of breastfeeding
The safety objectives of the study are to evaluate the safety of iron isomaltoside 1000 com-pared to RBC transfusion by
• Adverse events (AEs)
• Vital signs
• Biochemical safety parameters
Other objectives
• Maternal milk iron level
• Anaemia and gastrointestinal symptoms
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria:
A subject will be eligible for inclusion in the study if they fulfil the following criteria:
1. PPH > 1000 mL
2. Hb ≥ 5.5 and ≤ 8.0 g/dL (≥ 3.5 and ≤ 5.0 mmol/L)
3. Willingness to participate and signed the informed consent form
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E.4 | Principal exclusion criteria |
Exclusion criteria:
A subject will NOT be eligible for inclusion in this study if they fulfil any of the following criteria:
1. Women aged < 18 years
2. Multiple births
3. Peripartum RBC transfusion
4. Known iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemosiderosis)
5. Known hypersensitivity to parenteral iron or any excipients in the investigational drug products
6. Women with a history of active asthma within the last 5 years or a history of multiple allergies
7. Known decompensated liver cirrhosis or active hepatitis
8. Women with HELLP (Haemolysis Elevated Liver enzymes Low Platelet count) syn-drome (defined according to Dansk Selskab for Obstetrik og Gynækologi guidelines)
9. Active acute infection assessed by clinical judgement
10. Rheumatoid arthritis with symptoms or signs of active joint inflammation
11. History of anaemia caused by e. g. thalassemia, hypersplenism or haemolytic anaemia (known haematologic disorder other than iron deficiency)
12. Not able to read, speak and understand the Danish language
13. Participation in any other clinical study where the study drug has not passed 5 half-lives prior to the baseline
14. Any other medical condition that, in the opinion of Investigator, may cause the patient to be unsuitable for completion of the study or place the patient at potential risk from being in the study. For example, a malignancy, uncontrolled hypertension, unstable ischaemic heart disease or uncontrolled diabetes mellitus
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is to measure and compare the aggregated change in phys-ical fatigue score from baseline to week 12 (area under the curve (AUC)) in the two treatment arms measured by the Multidimensional Fatigue Inventory (MFI). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline till week 12. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are to measure and compare the following in the two treatment arms
• Change in Hb concentration from baseline to day 1, 2, 3, 4, 5, 6 and 7, week 3, 8 and 12
• Proportion of women who achieve Hb levels of > 10 g/dL (6.2 mmol/L) at any time
• Proportion of women who achieve increase from baseline in Hb concentration ≥ 2.0 g/dL (1.2 mmol/L) at any time
• Change in concentrations of p-ferritin, p-iron, p-transferrin, transferrin saturation (TSAT), reticulocyte count and mean reticulocyte haemoglobin content (CHr) from baseline to day 1, 2, 3, 4, 5, 6 and 7, week 3, 8 and 12
• Change in MFI physical fatigue symptoms from baseline to day 1, 2, 3, 4, 5, 6 and 7, week 3, 8 and 12
• Change in other MFI fatigue symptoms from day 3 to week 1, 3, 8 and 12
• Change in fatigue symptoms measured by the postpartum questionnaire from baseline to day 1, 2, 3, 4, 5, 6 and 7, week 3, 8 and 12
• Change in postpartum depression symptoms measured by the Edinburgh Postnatal Depression Scale (EPDS) from week 1 to 3, 8 and 12
• Time to postpartum lactogenesis
• Time to discontinuation of breastfeeding
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please see secondary endpoints for timepoints. |
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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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Red Blood Cell Transfusion |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |