Fetal and Neonatal Alloimmune ThrombocytopeniaHIPNCT04067375
Towards Routine HPA-screening In Pregnancy to Prevent FNAIT
An observational study of Fetal and Neonatal Alloimmune Thrombocytopenia, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is the most common cause of severe thrombocytopenia in otherwise healthy born neonates. FNAIT results in a risk of bleeding the most severe complication being intracranial haemorraghes (ICH). Bleedings can be prevented by effective antental treatment. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Fetal and Neonatal Alloimmune Thrombocytopenia
- What is being tested?
- Clinical data collection.
- Type of treatment
- Vaccines
- How many people
- 3,660 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Mar 2017to 1 Apr 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Pregnant women.
Who may be able to join
- All pregnant women, of whom routine blood samples are taken at 27 weeks gestational age (GA).
Who cannot join
- There are no predefined exclusion criteria, since we are aiming to determine the incidence in the complete pregnant population in the Netherlands.
- [ WILSONBEKWAAM EXCLUSIE]
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Towards Routine HPA-screening in Pregnancy to Prevent FNAIT: Assessing Disease Burden and Optimising Risk Group Selection
Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is the most common cause of severe thrombocytopenia in otherwise healthy born neonates. FNAIT results in a risk of bleeding the most severe complication being intracranial haemorraghes (ICH). Bleedings can be prevented by effective antental treatment. In the absence of screening programs this treatment is too late to prevent the first affected child. The investigators aim to identify the pregnancies at risk and describe the incidence and natural course of this disease. In this way fetuses at risk can be identified in the future and timely antenatal treatment can be initiated.
Read the detailed description
Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is the most common cause of severe thrombocytopenia in neonates. It is an immunological process, in which Human Platelet Antigen (HPA) alloantibodies produced by the mother can cross the placenta and target fetal platelets. The most frequent alloantigen to elicit platelet-reactive antibody responses is HPA-1a. The resulting low platelet count in the fetus or neonate correlates with an increased risk of bleeding complications and severe adverse outcome, defined as perinatal death or intracranial haemorrhage (ICH). This can lead to life-long handicaps, cerebral palsy, cortical blindness and mental retardation. One in 50 pregnancies is at risk for FNAIT, since 2,1% of the Caucasian population is HPA-1a negative. Alloantibodies are calculated to be present in 1:400 pregnancies, leading to FNAIT-related severe adverse outcome in at least 1:1300 fetuses or neonates, and this is likely an underestimation. There is a highly effective antenatal treatment available for preventing these severe adverse outcomes, consisting of weekly injection of intravenous immunoglobulins (IvIG). Unfortunately, in the current practice, this treatment can only be applied in subsequent pregnancies with known alloimmunization, after a symptomatic sibling leading to diagnosis of the disease. In potential future antenatal screening for HPA-alloantibodies, all pregnancies at risk can be identified in time, to start antenatal treatment and reduce severe adverse outcomes. However, before such a program can be realised, detailed information about incidence and natural course of the disease is needed. Furthermore, laboratory tests to identify fetuses at high risk to prevent overtreatment are needed, since approximately 10-30% of the HPA alloimmunized cases result in severe thrombocytopenia and clinically relevant disease.
Objectives:
- The main objective of this study is to assess the incidence and severity of FNAIT and bleeding complications (including ICH) among neonates.
- To develop a screening platform, including diagnostic assay(s) to identify fetuses at high risk for bleeding complications due to FNAIT.
Study design: Prospective observational cohort
Study population: Pregnant women
Main study parameters/endpoints: The main study parameters are HPA-1a alloantibodies, clinically relevant FNAIT. Secondary parameters include: neonatal outcome (bleeding signs other than ICH, treatment for thrombocytopenia, morbidity).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: These pregnant women participate in the national antenatal screening programme for Prevention and Screening of Infectious diseases and Erythrocyte Immunisation (PSIE) and have a routine blood sampling at 27th week of gestation. This blood sample will be used this to perform all necessary tests, so no additional (medical) procedures will be performed. Additionally, after delivery clinical data concerning the pregnancy, delivery and the health of the child in the first postnatal period are collected by questioning the obstetric health care provider.
- Being tested
- Clinical data collection.
- Medical subject headings
- Thrombocytopenia, Neonatal Alloimmune
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical data collection.Other
The following clinical data will be collected; maternal baseline characteristics, delivery related data, neonatal outcome, neonatal bleeding signs.
| Study group | Role | What they receive |
|---|---|---|
| Pregnant women, HPA-1a positive | RhD or Rhc negative women, identified through prenatal screening for red cell alloimmunization, that are typed as HPA-1a positive. Receives: Other: Clinical data collection. | |
| Pregnant women, HPA-1a negative with HPA-1a alloantibodies | RhD or Rhc negative women, identified through prenatal screening for red cell alloimmunization, that are typed as HPA-1a negative and have formed anti-HPA-1a alloantibodies. Receives: Other: Clinical data collection. | |
| Pregnant women, HPA-1a negative without HPA-1a alloantibodies | RhD or Rhc negative women, identified through prenatal screening for red cell alloimmunization, that are typed as HPA-1a negative and did not have formed anti-HPA-1a alloantibodies. Receives: Other: Clinical data collection. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical relevant FNAIT
Incidence of HPA-1a mediated FNAIT. defined as severe or mild FNAIT
Severe: Intracranial haemorrhage or Internal organ haemorrhage Mild: petechiae, hematoma, purpura or mucosal bleeding.Thrombocytopenia for platelet transfusion, IVIg or clinical observation.
Measured: Within 7 days after birth.
Secondary outcomes (3)
Neonatal thrombocytopenia
Thrombocytopenia: platelet count <150 x10^9/L Moderate thrombocytopenia: platelet count <100 x10^9/L Severe thrombocytopenia: platelet count <50 x10^9/L Extremely severe thrombocytopenia: platelet count <20 x10^9/L
Measured: Within 7 days after birth.
Neonatal infection
CRP >10 and positive blood culture, for which antibiotics are administerd
Measured: Within 7 days after birth.
Chromosomal abnormality
Chromosomal abnormalities as measured by DNA assessment (karyotyping, array, WGS/WES)
Measured: Within 7 days after birth.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2019
- Study start1 Mar 2017
- Primary completion1 Apr 2020
- Study completion1 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Fetal and Neonatal Alloimmune ThrombocytopeniaStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 3,660 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Sanquin Research & Blood Bank Divisions, Landsteiner Foundation for Blood Transfusion
- Responsible party
- Principal investigator, DickOepkes, Leiden University Medical Center
- Investigators
- Dick Oepkes, Prof MD PhD, Study director, Department of Obstetrics, Leiden University Medical Centre, LeidenMasja de Haas, Prof MD PhD, Study director, Department of Immunohematology Diagnostics, Sanquin Diagnostics, AmsterdamEllen vd Schoot, Prof MD PhD, Study director, Department of Experimental Immunohematology, Sanquin Reseach, Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04067375
- Sponsor's protocol ID
- P16.002
- Acronym
- HIP
- Status last verified
- Sep 2020
- First submitted
- 16 Jul 2019
- Last updated
- 2 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No information will be given about individual participant data to the participating pregnant women, nor the obstetric caregiver will be informed about the serological HPA-1a typing results. Also, we decided to perform the antibody detection test after birth. Thus no additional information can be known that would otherwise change the management of the current pregnancy, according to the Dutch Guidelines.
Publications
de Vos TW, Winkelhorst D, Porcelijn L, Beaufort M, Oldert G, van der Bom JG, Lopriore E, Oepkes D, de Haas M, van der Schoot E. Natural history of human platelet antigen 1a-alloimmunised pregnancies: a prospective observational cohort study. Lancet Haematol. 2023 Dec;10(12):e985-e993. doi: 10.1016/S2352-3026(23)00271-5. Epub 2023 Oct 27.
PubMed 38407610Winkelhorst D, de Vos TW, Kamphuis MM, Porcelijn L, Lopriore E, Oepkes D, van der Schoot CE, de Haas M. HIP (HPA-screening in pregnancy) study: protocol of a nationwide, prospective and observational study to assess incidence and natural history of fetal/neonatal alloimmune thrombocytopenia and identifying pregnancies at risk. BMJ Open. 2020 Jul 20;10(7):e034071. doi: 10.1136/bmjopen-2019-034071.
PubMed 32690731
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Towards Routine HPA-screening in Pregnancy to Prevent FNAIT: Assessing Disease Burden and Optimising Risk Group Selection
- ClinicalTrials.gov ID
- NCT04067375
- Acronym / sponsor ID
- HIP / P16.002
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3,660 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Sanquin Research & Blood Bank Divisions, Landsteiner Foundation for Blood Transfusion
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 1 Apr 2020 (actual)
- Study completion
- 1 Apr 2020 (actual)
- First posted
- 26 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is the most common cause of severe thrombocytopenia in otherwise healthy born neonates. FNAIT results in a risk of bleeding the most severe complication being intracranial haemorraghes (ICH). Bleedings can be prevented by effective antental treatment. In the absence of screening programs this treatment is too late to prevent the first affected child. The investigators aim to identify the pregnancies at risk and describe the incidence and natural course of this disease. In this way fetuses at risk can be identified in the future and timely antenatal treatment can be initiated.
Detailed description
Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is the most common cause of severe thrombocytopenia in neonates. It is an immunological process, in which Human Platelet Antigen (HPA) alloantibodies produced by the mother can cross the placenta and target fetal platelets. The most frequent alloantigen to elicit platelet-reactive antibody responses is HPA-1a. The resulting low platelet count in the fetus or neonate correlates with an increased risk of bleeding complications and severe adverse outcome, defined as perinatal death or intracranial haemorrhage (ICH). This can lead to life-long handicaps, cerebral palsy, cortical blindness and mental retardation. One in 50 pregnancies is at risk for FNAIT, since 2,1% of the Caucasian population is HPA-1a negative. Alloantibodies are calculated to be present in 1:400 pregnancies, leading to FNAIT-related severe adverse outcome in at least 1:1300 fetuses or neonates, and this is likely an underestimation. There is a highly effective antenatal treatment available for preventing these severe adverse outcomes, consisting of weekly injection of intravenous immunoglobulins (IvIG). Unfortunately, in the current practice, this treatment can only be applied in subsequent pregnancies with known alloimmunization, after a symptomatic sibling leading to diagnosis of the disease. In potential future antenatal screening for HPA-alloantibodies, all pregnancies at risk can be identified in time, to start antenatal treatment and reduce severe adverse outcomes. However, before such a program can be realised, detailed information about incidence and natural course of the disease is needed. Furthermore, laboratory tests to identify fetuses at high risk to prevent overtreatment are needed, since approximately 10-30% of the HPA alloimmunized cases result in severe thrombocytopenia and clinically relevant disease.
Objectives:
- The main objective of this study is to assess the incidence and severity of FNAIT and bleeding complications (including ICH) among neonates.
- To develop a screening platform, including diagnostic assay(s) to identify fetuses at high risk for bleeding complications due to FNAIT.
Study design: Prospective observational cohort
Study population: Pregnant women
Main study parameters/endpoints: The main study parameters are HPA-1a alloantibodies, clinically relevant FNAIT. Secondary parameters include: neonatal outcome (bleeding signs other than ICH, treatment for thrombocytopenia, morbidity).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: These pregnant women participate in the national antenatal screening programme for Prevention and Screening of Infectious diseases and Erythrocyte Immunisation (PSIE) and have a routine blood sampling at 27th week of gestation. This blood sample will be used this to perform all necessary tests, so no additional (medical) procedures will be performed. Additionally, after delivery clinical data concerning the pregnancy, delivery and the health of the child in the first postnatal period are collected by questioning the obstetric health care provider.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pregnant women, HPA-1a positive | – | Other: Clinical data collection.RhD or Rhc negative women, identified through prenatal screening for red cell alloimmunization, that are typed as HPA-1a positive. |
| Pregnant women, HPA-1a negative with HPA-1a alloantibodies | – | Other: Clinical data collection.RhD or Rhc negative women, identified through prenatal screening for red cell alloimmunization, that are typed as HPA-1a negative and have formed anti-HPA-1a alloantibodies. |
| Pregnant women, HPA-1a negative without HPA-1a alloantibodies | – | Other: Clinical data collection.RhD or Rhc negative women, identified through prenatal screening for red cell alloimmunization, that are typed as HPA-1a negative and did not have formed anti-HPA-1a alloantibodies. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Pregnant women.
Key inclusion criteria (1 listed)
- All pregnant women, of whom routine blood samples are taken at 27 weeks gestational age (GA).
Key exclusion criteria (2 listed)
- There are no predefined exclusion criteria, since we are aiming to determine the incidence in the complete pregnant population in the Netherlands.
- [ WILSONBEKWAAM EXCLUSIE]
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinical data collection.The following clinical data will be collected; maternal baseline characteristics, delivery related data, neonatal outcome, neonatal bleeding signs. | Other | Pregnant women, HPA-1a negative with HPA-1a alloantibodies, Pregnant women, HPA-1a negative without HPA-1a alloantibodies, Pregnant women, HPA-1a positive |
Primary outcome
Clinical relevant FNAIT
Time frame: Within 7 days after birth.
Incidence of HPA-1a mediated FNAIT. defined as severe or mild FNAIT Severe: Intracranial haemorrhage or Internal organ haemorrhage Mild: petechiae, hematoma, purpura or mucosal bleeding.Thrombocytopenia for platelet transfusion, IVIg or clinical observation.
3 secondary outcomes
Neonatal thrombocytopenia
Time frame: Within 7 days after birth.
Neonatal infection
Time frame: Within 7 days after birth.
Chromosomal abnormality
Time frame: Within 7 days after birth.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2020.
- Derived from this study: PubMed 38407610de Vos TW, Winkelhorst D, Porcelijn L, Beaufort M, Oldert G, van der Bom JG, Lopriore E, Oepkes D, de Haas M, van der Schoot E. Natural history of human platelet antigen 1a-alloimmunised pregnancies: a prospective observational cohort study. Lancet Haematol. 2023 Dec;10(12):e985-e993. doi: 10.1016/S2352-3026(23)00271-5. Epub 2023 Oct 27.
- Derived from this study: PubMed 32690731Winkelhorst D, de Vos TW, Kamphuis MM, Porcelijn L, Lopriore E, Oepkes D, van der Schoot CE, de Haas M. HIP (HPA-screening in pregnancy) study: protocol of a nationwide, prospective and observational study to assess incidence and natural history of fetal/neonatal alloimmune thrombocytopenia and identifying pregnancies at risk. BMJ Open. 2020 Jul 20;10(7):e034071. doi: 10.1136/bmjopen-2019-034071.
- Individual participant dataSharing planned: No. No information will be given about individual participant data to the participating pregnant women, nor the obstetric caregiver will be informed about the serological HPA-1a typing results. Also, we decided to perform the antibody detection test after birth. Thus no additional information can be known that would otherwise change the management of the current pregnancy, according to the Dutch Guidelines.
Related trials for Fetal and Neonatal Alloimmune Thrombocytopenia
RecruitingPhase 3
A Study of Nipocalimab or Intravenous Immunoglobulin (IVIG) in Pregnancies At Risk of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)
Thrombocytopenia, Neonatal Alloimmune
RecruitingPhase 3
A Study of Nipocalimab in Reducing the Risk of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)
Thrombocytopenia, Neonatal Alloimmune
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dick Oepkes, Prof MD PhD study director
Department of Obstetrics, Leiden University Medical Centre, Leiden
Masja de Haas, Prof MD PhD study director
Department of Immunohematology Diagnostics, Sanquin Diagnostics, Amsterdam
Ellen vd Schoot, Prof MD PhD study director
Department of Experimental Immunohematology, Sanquin Reseach, Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fetal and Neonatal Alloimmune Thrombocytopenia, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical relevant FNAIT (time frame: Within 7 days after birth.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04067375, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2020.