Treatment of Women After Postpartum Haemorrhage (PP-01)

A, Randomized Comparative, Open-Label Study of Intravenous Iron Isomaltoside 1000 (Monofer®) Administered by High Single Dose In-fusions or Standard Medical Care in Women After Postpartum Haemorrhage

The primary purpose of this study is to compare the efficacy of IV high single dose infusion of iron isomaltoside 1000 to standard medical care in women with PPH evaluated as physical fatigue.

Study Overview

• Status: Completed
• Conditions: Postpartum Haemorrhage
• Intervention / Treatment: Drug: Iron isomaltoside 1000; Other: Standard medical Care

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women with PPH ≥ 700 and ≤ 1000 mL or PPH > 1000 mL and Hb > 6.5 g/dL (4.0 mmol/L) measured > 12 hours after delivery
2. Willingness to participate and signed the informed consent form

Exclusion 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 and active hepatitis
8. Women with HELLP (Haemolysis Elevated Liver enzymes Low Platelet count) syndrome (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 the 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Iron isomaltoside 1000 (Monofer®)	Drug: Iron isomaltoside 1000; A single dose of 1200 mg iron isomaltoside 1000 is given. The dose is diluted in 100 ml 0.9 % sodium chloride and given over approximately 15 min.; Other Names: Monofer®
ACTIVE_COMPARATOR: Standard medical Care	Other: Standard medical Care; Standard medical Care is most often to recommend women with PPH to continue oral iron supplementation as recommended during pregnancy or to advise the subject to take 100 mg oral iron 1-2 times a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical fatigue	The primary objective of this study is to compare efficacy of IV high single dose infusion of iron isomaltoside 1000 to standard medical care in women with PPH evaluated as physical fatigue.	From exposure to 12 weeks post-exposure

Secondary Outcome Measures

Outcome Measure	Time Frame
Breastfeeding	From exposure to 12 weeks post-exposure
Change in Hb concentration	From exposure to week 1, 3, 8 and 12 post-exposure
Change in concentrations of p-ferritin	From exposure to day 3, week 1, 3, 8 and 12 post-exposure
Change in Fatigue symptoms	From exposure to day 3, week 1, 3, 8 and 12 post-exposure
Change in postpartum depression symptoms	From exposure to 12 weeks post-exposure
RCB transfusions	From exposure to 12 weeks post-exposure
Adverse drug reactions (ADRs)	From exposure to day 3, week 1, 3, 8 and 12 post-exposure
Change in concentrations of p-iron	From exposure to day 3, week 1, 3, 8 and 12 post-exposure
Change in concentrations of p-transferrin	From exposure to day 3, week 1, 3, 8 and 12 post-exposure
Change in concentrations of transferrin saturation (TSAT)	From exposure to day 3, week 1, 3, 8 and 12 post-exposure
Change in concentrations of reticulocyte count	From exposure to day 3, week 1, 3, 8 and 12 post-exposure
Change in concentrations of mean reticulocyte haemoglobin content (CHr)	From exposure to day 3, week 1, 3, 8 and 12 post-exposure
Change in haematology parameters	From exposure to day 3, week 1, 3, 8 and 12 post-exposure

Other Outcome Measures

Outcome Measure	Time Frame
Change in anaemia symptoms	From exposure to day 3, week 1, 3, 8 and 12 post-exposure
Change in gastrointestinal symptoms	From exposure to day 3, week 1, 3, 8 and 12 post-exposure

Collaborators and Investigators

• Sponsor: Pharmacosmos A/S
• Collaborators: BioStata

Publications and helpful links

General Publications

• Holm C, Thomsen LL, Langhoff-Roos J. Intravenous iron isomaltoside treatment of women suffering from severe fatigue after postpartum hemorrhage. J Matern Fetal Neonatal Med. 2019 Sep;32(17):2797-2804. doi: 10.1080/14767058.2018.1449205. Epub 2018 Mar 20.
• Holm C, Thomsen LL, Norgaard A, Langhoff-Roos J. Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage: study protocol for a randomised controlled trial. Trials. 2015 Jan 14;16:5. doi: 10.1186/1745-6215-16-5.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: July 4, 2013
• First Posted (ESTIMATE): July 10, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): April 29, 2015
• Last Update Submitted That Met QC Criteria: April 28, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Hematinics; Iron isomaltoside 1000
• Other Study ID Numbers: PP-01