Observational study of blood transfusions in European preterm infants
| ISRCTN | ISRCTN17267090 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17267090 |
| Secondary identifying numbers | G21.207 |
- Submission date
- 29/11/2022
- Registration date
- 02/12/2022
- Last edited
- 27/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Neonatal Diseases
Plain English summary of protocol
Background and study aims
The aim of this study is to learn more about the use of blood transfusions in the neonatal intensive care unit. Most premature babies in the neonatal intensive care unit receive a blood product during their admission. Unfortunately, there are no international transfusion guidelines for this patient group that are used by Europe as a whole. There may be a great deal of variation between doctors when they decide to administer a blood product. To investigate this, researchers are collecting information on how many preterm babies receive a blood transfusion and why they did or did not receive a blood transfusion. The results of this study will help to improve the use of blood transfusion in preterm babies in Europe.
Who can participate?
Babies born below 32 weeks of gestation who are admitted to a participating center during the 6 weeks of the study
What does the study involve?
All participating neonatal intensive care units will collect information on blood transfusions for a period of 6 weeks. The study requires the collection and use of the participating child's medical and personal data. This is necessary to answer the research questions of the study. The researchers will only collect data from the child's (electronic) patient record, including gender, gestational age, date of birth and birthweight, and data on any blood transfusions the child may receive during admission. The researchers will only collect information from laboratory tests that are part of the regular treatment in the neonatal intensive care unit. To protect the child's privacy, each child will be given a study code that will appear on the data. The personal data that can identify the child will be converted. Only the local researcher knows which study code the child has. The key to the study code remains with the local researcher. The study data will be safely stored in an encrypted (coded) electronic database to ensure proper use and data protection. The researchers will store the data for 15 years.
What are the possible benefits and risks of participating?
Participating will contribute to more knowledge on the blood transfusions given during admission to the neonatal intensive care unit. The study does in no way influence the care the child receives. No additional measurements will be taken during this study. There are no negative consequences, other disadvantages, or risks for the child participating in this study.
Where is the study run from?
Leiden University Medical Center (Netherlands)
When is the study starting and how long is it expected to run for?
January 2021 to September 2023
Who is funding the study?
1. Sanquin Blood Supply Foundation
2. European Society for Pediatric Research (ESPR)
3. European Blood Alliance (EBA)
Who is the main contact?
Nina Houben, INSPIRE@lumc.nl
Contact information
Scientific
Albinusdreef 2
Leiden
2333ZA
Netherlands
 ORCID ID |
0000-0001-7605-4927 |
|---|---|
| Phone | Not applicable |
| INSPIRE@lumc.nl |
Study information
| Study design | International multicenter prospective observational point prevalence study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Other |
| Scientific title | International Neonatal tranSfusion PoInt pREvalence study |
| Study acronym | INSPIRE |
| Study objectives | Premature neonates are a highly transfused patient group, though robust evidence supporting neonatal transfusion practice is scarce. Two randomized trials indicated no benefit in long-term outcomes of liberal compared to restrictive thresholds for red blood cell (RBC) transfusions. Another randomized trial, comparing a high and low platelet transfusion threshold, even reported evidence that transfusions can cause harm. No neonatal transfusion guidelines have been implemented by Europe as a whole, resulting in significant variation in transfusion practice. Detailed contemporary data on neonatal transfusion practice in Europe is lacking. |
| Ethics approval(s) | On 31/03/2022 the Medical Research Ethics Committee Leiden Den Haag Delft (2300 RC Leiden, the Netherlands; +31(0) 71 – 5265106; metc-ldd@lumc.nl) confirmed that the research protocol "INSPIRE-study: International Neonatal tranSfusion PoInt pREvalence", reference number G21.207 does not apply to the Medical Research Involving Human Subjects Act (Dutch abbreviation: WMO). Therefore, it is exempt from review by the Committee. |
| Health condition(s) or problem(s) studied | The use of blood transfusion in European preterm infants |
| Intervention | In this international, multicenter, prospective, observational point prevalence study, the researchers will include neonates with gestational age at birth <32 weeks admitted to a participating tertiary-level neonatal intensive care unit (NICU). Data will be collected over a 1-year period, in which each NICU will collect data for 6 weeks. Data will be collected from the hospital’s written or electronic patient record files, recorded imaging reports, hospital blood bank records, and nurses’ records. |
| Intervention type | Other |
| Primary outcome measure | 1. The prevalence and incidence of RBC, platelet, and plasma transfusions in neonates with a gestational age of less than 32 weeks at birth, admitted to a tertiary-level NICU: 1.1. The prevalence is calculated by dividing the number of transfusions of the respective transfusion type by the total sum of neonate study days 1.2. The incidence of receiving at least one transfusion, both for any transfusion as per transfusion type, is calculated by dividing the number of neonates receiving at least one transfusion by the total sum of neonate study days Each participating center will collect data during a 6-week period, in which they will screen all 7 days of these weeks for the study outcomes in the included neonates. For neonates already admitted at the start of the study, the start of patient follow-up in the study is equal to the first day of the study period in the participating center. For all other included infants, the start of patient follow-up equals the day of admission. The end of patient follow-up in the study is equal to the day of death, the day of transfer, the day of discharge, or the last day of the study period in the center (whichever occurs first). |
| Secondary outcome measures | 1. Variations in prevalence rates of RBC, platelet, and plasma transfusions. Data analysis will be predominantly descriptive, comparing both participating countries and different types of NICUs. Types of NICUs will be defined based on unit size and whether surgical procedures are being performed. 2. Indications for transfusion: the primary indication for which the transfusion is prescribed by the treating physician will be collected. If applicable, the secondary and tertiary indications will also be registered, as clinicians may consider multiple factors when deciding to give a transfusion. For each transfusion, the prescribing physician must choose from a list of predefined indications (up to three options can be selected, ranked primary to tertiary indication). The primary indication is the indication that has the most weight in the decision to prescribe a transfusion. If the indication for transfusion is registered by someone other than the prescribing physician, the prescribing physician must confirm the correctness of these data. 3. Duration, volume, and transfusion rate of the prescribed RBC, platelet, and plasma transfusions 4. Guideline use: data is collected on whether centers have guidelines in place regarding RBC, platelet, and plasma transfusion for neonates. Following the implementation model by Wensing and Grol, information is gathered on the implementation of transfusion guidelines. Additionally, the researchers will ask centers with established guidelines to provide the guidelines in place at the start of data collection. The researchers will analyse how many of the RBC and platelet guidelines have already incorporated the results of recent clinical trials. They will categorize the existing RBC guidelines into “TOP and/or ETTNO incorporated” and “TOP and/or ETTNO not incorporated”. They will categorize the existing platelet guidelines into “PlaNeT-2/MATISSE incorporated” and “PlaNeT-2/MATISSE not incorporated”. They will assess to what extent centers follow their own local and/or national guidelines. 5. Evidence-basedness of practice: before the start of data collection, the researchers will collaborate with various experts to define what they view as high-quality evidence regarding RBC and platelet transfusion practices in neonates, using the best available evidence including the TOP, ETTNO, and PlaNeT-2/MATISSE trials. They will assess if the RBC and platelet transfusions were prescribed following the best available evidence, by categorizing the prescribed transfusions into different levels of certainty in evidence. They will assign a panel review by three ‘blinded’ experts to discuss cases where there may be ambiguity on the certainty of evidence to support transfusion practice. Transfusion events in clinical scenarios that were not addressed in randomized trials will not be assessed. 6. Transfusion-associated adverse effects: in the absence of clear definitions of transfusion-associated side effects in neonates, the researchers will ask participating centers to register any perceived transfusion-associated adverse effects if the local investigators consider the adverse event to be potentially associated with the preceding transfusion. With this they hope to gain insight into what adverse effects neonatologists identify in clinical practice, despite the lack of well-defined descriptions. 7. Component specifications: the researchers will perform an online survey among transfusion experts in which they explore variations in transfusion component characteristics. They chose this strategy because neonatologists may not be aware of all relevant component specifications. The survey will be sent to transfusion experts in all countries participating in this study during the data collection period. The researchers will record the blood banks from which each participating NICU receives their blood products, which will allow them to link the NICU clinical data to the component specifications reported by the transfusion specialists. They aim to include all blood banks that provide blood products to participating NICUs in the survey. 8. Transfusion with blood products other than RBC, platelet, and plasma or agents that promote or reduce coagulation. The researchers will collect data on transfusions of blood products other than RBC, platelet, and plasma transfusions or agents that promote or reduce coagulation, such as erythropoietin. They will describe these treatments and the indications for which they were prescribed. Each participating center will collect data during a 6-week period, in which they will screen all 7 days of these weeks for the study outcomes in the included neonates. For neonates already admitted at the start of the study, the start of patient follow-up in the study is equal to the first day of the study period in the participating center. For all other included infants, the start of patient follow-up equals the day of admission. The end of patient follow-up in the study is equal to the day of death, the day of transfer, the day of discharge, or the last day of the study period in the center (whichever occurs first). |
| Overall study start date | 01/01/2021 |
| Completion date | 30/09/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Both |
| Target number of participants | 520 |
| Total final enrolment | 1143 |
| Key inclusion criteria | A potential subject who meets both of the following criteria can be included in this study: 1. Admission to a participating tertiary level NICU during the study period (note: this also includes neonates who are admitted to the NICU prior to the start of the study period, born outside the NICU institute of admission and/or readmitted to the NICU) 2. Gestational age at birth below 32 weeks (note: the postmenstrual age [PMA; gestational age + chronological age] at admission can be ≥32+0 weeks, however the PMA at inclusion cannot exceed 44+0 weeks) |
| Key exclusion criteria | Does not meet the inclusion criteria |
| Date of first enrolment | 26/09/2022 |
| Date of final enrolment | 31/08/2023 |
Locations
Countries of recruitment
- Austria
- Bosnia and Herzegovina
- Croatia
- Czech Republic
- Denmark
- England
- France
- Germany
- Hungary
- Ireland
- Italy
- Netherlands
- Norway
- Poland
- Portugal
- Romania
- Slovakia
- Slovenia
- Spain
- Sweden
- Switzerland
Study participating centres
Leiden
2333 ZA
Netherlands
Netherlands
Sponsor information
Hospital/treatment centre
Albinusdreef 2
Leiden
2333ZA
Netherlands
| Phone | +31 (0)71 526 91 11 |
|---|---|
| infowakz@lumc.nl | |
| Website | https://www.lumc.nl/ |
"ROR" |
https://ror.org/05xvt9f17 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Sanquin Blood Supply Foundation
- Location
- Netherlands
No information available
No information available
Results and Publications
| Intention to publish date | 31/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in open-access peer-reviewed international scientific journals, results will also be published in a PhD thesis. |
| IPD sharing plan | The coded datasets generated during and/or analyses during the current study are not expected to be made available. The dataset will be exclusively accessible for the involved researchers and restrictions apply to the availability of these data as underlined in the data sharing agreement. The database shall be jointly owned by the parties involved, and participating centres have the right to apply to use the dataset for their own research proposal(s). External applications for access will be assessed by the principal investigators after the prior written consent of all parties involved. The dataset will be stored in a Leiden University Medical Center ProMISe Datasafe. ProMISe meets the requirements for data safety and privacy as set by international law and the security conditions as demanded by GCP. The ProMISe Datasafe automatically makes back-ups twice a day. Data will be stored for the length of the study and 15 years afterwards. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | 30/11/2022 | No | No | ||
| Protocol file | version 3 | 11/03/2022 | 30/11/2022 | No | No |
| Statistical Analysis Plan | Red Blood Cell Transfusion Paper version 6 |
21/12/2023 | 26/01/2024 | No | No |
| Statistical Analysis Plan | Plasma Transfusion Paper version 1 |
19/04/2024 | 08/07/2024 | No | No |
| Statistical Analysis Plan | Platelet Transfusion Paper version 1 |
29/01/2023 | 08/07/2024 | No | No |
| Results article | 03/09/2024 | 27/11/2024 | Yes | No | |
| Results article | Platelet transfusion | 10/10/2024 | 27/11/2024 | Yes | No |
| Results article | Plasma transfusions | 19/01/2025 | 27/01/2025 | Yes | No |
Additional files
- 42833_PROTOCOL.pdf
- 42833_PROTOCOL_V3_11Mar22.pdf
- ISRCTN17267090_SAP_V6_21Dec23.pdf
- Red Blood Cell Transfusion Paper
- ISRCTN17267090 SAP_Plasma_v1 19Apr2024.pdf
- Plasma Transfusion Paper
- ISRCTN17267090 SAP_Platelet_v1 29Jan2023_signed.pdf
- Platelet Transfusion Paper
Editorial Notes
27/01/2025: Publication reference added.
27/11/2024: Publication reference added.
08/07/2024: Two other statistical analysis plans were uploaded as additional files.
26/01/2024: Statistical analysis plan and total final enrolment added.
25/08/2023: The overall study end date was changed from 31/08/2023 to 30/09/2023.
30/11/2022: Trial's existence confirmed by the Medical Research Ethics Committee Leiden Den Haag Delft.
