Pyruvate Kinase DeficiencyPKD NHSNCT02053480
Pyruvate Kinase Deficiency Natural History Study
An observational study of Pyruvate Kinase Deficiency and Congenital Non-Spherocytic Hemolytic Anemia, run by Boston Children's Hospital at 30 sites in 6 countries.
Trial summary
The purpose of this study is to describe the range and incidence of symptoms, treatments, and complications related to pyruvate kinase deficiency (PKD). Eligible patients are those of all ages with known PKD or with a hemolytic anemia and a family member with PKD. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Pyruvate Kinase Deficiency, Congenital Non-Spherocytic Hemolytic Anemia
- How many people
- 254 participants
- Where
- 30 sitesin 6 countries
- Study dates
- Dec 2013to May 2020
- How long will I take part?
- 2 Years
- 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
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with Pyruvate Kinase Deficiency of all ages
Who may be able to join
- Patients of all ages with biochemically or genetically diagnosed PKD.
- Patients with a hemolytic anemia AND a family member with genetically diagnosed PKD
- The participant or the guardian of the participant is willing and able to give written informed consent and/or assent.
Who cannot join
- The participant or the guardian of the participant is unwilling or unable to give written informed consent and/or assent.
Trial locations and contacts
30 sites in 6 countries.
30 sites in 6 countries
United States19 sites
Children's Hospital of Atlanta
Atlanta, Georgia, 30342
Boston Children's Hospital
Boston, Massachusetts, 02115
University of Vermont College of Medicine & University of Vermont Medical Center
Burlington, Vermont, 05405
Lurie Children's Hospital
Chicago, Illinois, 60611
Nationwide Children's Hospital
Columbus, Ohio, 43205
Wayne State University School of Medicine
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine
Houston, Texas, 77030
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Children's Mercy Hospitals & Clinics
Kansas City, Missouri, 64108
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
DDC Clinic for Special Needs Children
Middlefield, Ohio, 44062
Weill Cornell Medical College
New York, New York, 10065
Stanford University
Palo Alto, California, 94305
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85006
University of Utah
Salt Lake City, Utah, 84108
Central Pennsylvania Clinic
Strasburg, Pennsylvania, 17579
University of Massachusetts Medical Center
Worcester, Massachusetts, 01605
Germany5 sites
Charite Berlin
Berlin
University of Freiburg
Freiburg im Breisgau, 79106
UniversitätsKlinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin Klinik Kinderheilkunde III
Heidelberg, 69120
Klinikum Kassel
Kassel, 34125
Klinikum der Universität München, Center for Pediatric Hematology/Hemostaseology
Munich, 80337
Canada3 sites
McMaster University
Hamilton, Ontario, L8N 3Z5
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
University Health Network
Toronto, Ontario, M5G 2C4
Italy1 site
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
About this study
Official title: Pyruvate Kinase Deficiency (PKD) Natural History Study
The purpose of this study is to describe the range and incidence of symptoms, treatments, and complications related to pyruvate kinase deficiency (PKD). Eligible patients are those of all ages with known PKD or with a hemolytic anemia and a family member with PKD. The study will collect retrospective medical history, routine clinical care data, and quality of life measures at baseline and annually for patients with PKD.
Read the detailed description
The purpose of the Pyruvate Kinase Deficiency (PKD) Natural History Study is to describe the natural history of PKD and the range and incidence of symptoms, treatments, and complications related to PKD. The study will collect retrospective medical history and routine clinical care data at baseline and annually for patients with PKD. Patients without a genetic diagnosis will have a blood sample drawn for genetic diagnostic confirmation for research purposes. Understanding the clinical variation among participants with PKD, and assessing treatments specific to PKD and their outcomes will accelerate improvement in the care of patients with PKD. Understanding the natural history of PKD may be useful in the design of future interventional studies. Detailed genotypic and phenotypic characterization of the cohort will allow for continued in depth characterization of PKD. Finally, the PKD Natural History Study will identify interested participants for future PKD studies.
Primary Objectives:
- To estimate the transfusion burden in splenectomized and non-splenectomized participants with PKD.
- To establish a patient registry as a potential source for recruitment to future research studies in PKD.
Secondary Objectives:
- To determine if patient-reported outcomes, including quality of life and fatigue scales, are associated with age, genotype, hemoglobin nadir, and/or transfusion burden, overall and within the subgroups of splenectomized vs. non-splenectomized participants;
- To describe changes over time in the range of hemoglobin values and markers of hemolysis within individual participants and among participants with PKD;
- To estimate the incidence of past splenectomy and annual splenectomy rate, as treatment for PKD;
- To estimate the prevalence and severity and describe the treatment of hepatic and cardiac iron overload and its complications in PKD (liver, cardiac, growth defects, hypogonadotropic hypogonadism, and other endocrine defects). To describe the changes in these complications that may occur over time and by age group;
- To estimate the prevalence of co-morbidities associated with chronic hemolysis in PKD, to identify which co-morbidities are the most common, and to determine if the prevalence and/or severity of co-morbidities change over time and by age at the time of the first appearance of the co-morbidity;
- To determine pregnancy outcomes among participants with PKD;
- To describe genotypic and phenotypic variation among participants and explore genotype-phenotype correlation in PKD.
- Keywords
- pyruvate kinase deficiency, hemolytic anemia, anemia, enzymopathy, jaundice, splenectomy, health-related quality of life, Hematologic diseases
- Medical subject headings
- Pyruvate Kinase Deficiency of Red Cells, Anemia, Hemolytic, Anemia, Jaundice, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Pyruvate Kinase Deficiency | Patients of all ages with Pyruvate Kinase Deficiency |
What is being measured
The primary outcome is the main question the study is designed to answer.
transfusion burden in splenectomized and non-splenectomized participants
Measured: 12 weeks
Secondary outcomes (3)
patient-reported outcomes
EuroQoL-5D-5L, Functional Assessment of Cancer Therapy-Anemia (FACT-An), Pediatric Quality of Life Inventory 4.0 (pedsQL 4.0), Pediatric Functional Assessment of Chronic Illness-Fatigue (pedsFACIT-F), Patient Reported Outcomes Measurement Information System Fatigue (PROMIS Fatigue)
Measured: enrollment, annually, up to 2 years
changes over time in hemoglobin and markers of hemolysis
Measured: enrollment, annually, up to 2 years
prevalence and severity of iron overload
Measured: enrollment, annually, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2014 (estimated)
- Study startDec 2013
- Primary completionDec 2019
- Study completionMay 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pyruvate Kinase DeficiencyStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe 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
- 254 participants (actual)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Agios Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Rachael Grace, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02053480
- Sponsor's protocol ID
- P00010515
- Acronym
- PKD NHS
- Status last verified
- May 2020
- First submitted
- 28 Jan 2014
- Last updated
- 22 May 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Grace RF, Bianchi P, van Beers EJ, Eber SW, Glader B, Yaish HM, Despotovic JM, Rothman JA, Sharma M, McNaull MM, Fermo E, Lezon-Geyda K, Morton DH, Neufeld EJ, Chonat S, Kollmar N, Knoll CM, Kuo K, Kwiatkowski JL, Pospisilova D, Pastore YD, Thompson AA, Newburger PE, Ravindranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Kunz J, Sheth S, Rose MJ, Bradeen HA, Neu N, Guo D, Al-Sayegh H, London WB, Gallagher PG, Zanella A, Barcellini W. Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study. Blood. 2018 May 17;131(20):2183-2192. doi: 10.1182/blood-2017-10-810796. Epub 2018 Mar 16.
PubMed 29549173van Beers EJ, van Straaten S, Morton DH, Barcellini W, Eber SW, Glader B, Yaish HM, Chonat S, Kwiatkowski JL, Rothman JA, Sharma M, Neufeld EJ, Sheth S, Despotovic JM, Kollmar N, Pospisilova D, Knoll CM, Kuo K, Pastore YD, Thompson AA, Newburger PE, Ravindranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Verhovsek M, Kunz J, McNaull MA, Rose MJ, Bradeen HA, Addonizio K, Li A, Al-Sayegh H, London WB, Grace RF. Prevalence and management of iron overload in pyruvate kinase deficiency: report from the Pyruvate Kinase Deficiency Natural History Study. Haematologica. 2019 Feb;104(2):e51-e53. doi: 10.3324/haematol.2018.196295. Epub 2018 Sep 13. No abstract available.
PubMed 30213831Bianchi P, Fermo E, Lezon-Geyda K, van Beers EJ, Morton HD, Barcellini W, Glader B, Chonat S, Ravindranath Y, Newburger PE, Kollmar N, Despotovic JM, Verhovsek M, Sharma M, Kwiatkowski JL, Kuo KHM, Wlodarski MW, Yaish HM, Holzhauer S, Wang H, Kunz J, Addonizio K, Al-Sayegh H, London WB, Andres O, van Wijk R, Gallagher PG, Grace RFF. Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency. Am J Hematol. 2020 May;95(5):472-482. doi: 10.1002/ajh.25753. Epub 2020 Mar 6.
PubMed 32043619Al-Samkari H, van Beers EJ, Morton DH, Eber SW, Chonat S, Kuo KHM, Kollmar N, Wang H, Breakey VR, Sheth S, Sharma M, Forbes PW, Klaassen RJ, Grace RF. Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency. Blood Adv. 2022 Mar 22;6(6):1844-1853. doi: 10.1182/bloodadvances.2021004675.
PubMed 34470054
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pyruvate Kinase Deficiency (PKD) Natural History Study
- ClinicalTrials.gov ID
- NCT02053480
- Acronym / sponsor ID
- PKD NHS / P00010515
- Keywords
- pyruvate kinase deficiency, hemolytic anemia, anemia, enzymopathy, jaundice, splenectomy, health-related quality of life, Hematologic diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 254 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Agios Pharmaceuticals, Inc.
- Study start
- Dec 2013
- Primary completion
- Dec 2019 (actual)
- Study completion
- May 2020 (actual)
- First posted
- 3 Feb 2014 (estimated)
- 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.
The purpose of this study is to describe the range and incidence of symptoms, treatments, and complications related to pyruvate kinase deficiency (PKD). Eligible patients are those of all ages with known PKD or with a hemolytic anemia and a family member with PKD. The study will collect retrospective medical history, routine clinical care data, and quality of life measures at baseline and annually for patients with PKD.
Detailed description
The purpose of the Pyruvate Kinase Deficiency (PKD) Natural History Study is to describe the natural history of PKD and the range and incidence of symptoms, treatments, and complications related to PKD. The study will collect retrospective medical history and routine clinical care data at baseline and annually for patients with PKD. Patients without a genetic diagnosis will have a blood sample drawn for genetic diagnostic confirmation for research purposes. Understanding the clinical variation among participants with PKD, and assessing treatments specific to PKD and their outcomes will accelerate improvement in the care of patients with PKD. Understanding the natural history of PKD may be useful in the design of future interventional studies. Detailed genotypic and phenotypic characterization of the cohort will allow for continued in depth characterization of PKD. Finally, the PKD Natural History Study will identify interested participants for future PKD studies.
Primary Objectives:
- To estimate the transfusion burden in splenectomized and non-splenectomized participants with PKD.
- To establish a patient registry as a potential source for recruitment to future research studies in PKD.
Secondary Objectives:
- To determine if patient-reported outcomes, including quality of life and fatigue scales, are associated with age, genotype, hemoglobin nadir, and/or transfusion burden, overall and within the subgroups of splenectomized vs. non-splenectomized participants;
- To describe changes over time in the range of hemoglobin values and markers of hemolysis within individual participants and among participants with PKD;
- To estimate the incidence of past splenectomy and annual splenectomy rate, as treatment for PKD;
- To estimate the prevalence and severity and describe the treatment of hepatic and cardiac iron overload and its complications in PKD (liver, cardiac, growth defects, hypogonadotropic hypogonadism, and other endocrine defects). To describe the changes in these complications that may occur over time and by age group;
- To estimate the prevalence of co-morbidities associated with chronic hemolysis in PKD, to identify which co-morbidities are the most common, and to determine if the prevalence and/or severity of co-morbidities change over time and by age at the time of the first appearance of the co-morbidity;
- To determine pregnancy outcomes among participants with PKD;
- To describe genotypic and phenotypic variation among participants and explore genotype-phenotype correlation in PKD.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pyruvate Kinase Deficiency | – | –Patients of all ages with Pyruvate Kinase Deficiency |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with Pyruvate Kinase Deficiency of all ages
Key inclusion criteria (3 listed)
- Patients of all ages with biochemically or genetically diagnosed PKD.
- Patients with a hemolytic anemia AND a family member with genetically diagnosed PKD
- The participant or the guardian of the participant is willing and able to give written informed consent and/or assent.
Key exclusion criteria (1 listed)
- The participant or the guardian of the participant is unwilling or unable to give written informed consent and/or assent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
transfusion burden in splenectomized and non-splenectomized participants
Time frame: 12 weeks
3 secondary outcomes
patient-reported outcomes
Time frame: enrollment, annually, up to 2 years
changes over time in hemoglobin and markers of hemolysis
Time frame: enrollment, annually, up to 2 years
prevalence and severity of iron overload
Time frame: enrollment, annually, up to 2 years
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 22 May 2020.
- Background: PubMed 29549173Grace RF, Bianchi P, van Beers EJ, Eber SW, Glader B, Yaish HM, Despotovic JM, Rothman JA, Sharma M, McNaull MM, Fermo E, Lezon-Geyda K, Morton DH, Neufeld EJ, Chonat S, Kollmar N, Knoll CM, Kuo K, Kwiatkowski JL, Pospisilova D, Pastore YD, Thompson AA, Newburger PE, Ravindranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Kunz J, Sheth S, Rose MJ, Bradeen HA, Neu N, Guo D, Al-Sayegh H, London WB, Gallagher PG, Zanella A, Barcellini W. Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study. Blood. 2018 May 17;131(20):2183-2192. doi: 10.1182/blood-2017-10-810796. Epub 2018 Mar 16.
- Background: PubMed 30213831van Beers EJ, van Straaten S, Morton DH, Barcellini W, Eber SW, Glader B, Yaish HM, Chonat S, Kwiatkowski JL, Rothman JA, Sharma M, Neufeld EJ, Sheth S, Despotovic JM, Kollmar N, Pospisilova D, Knoll CM, Kuo K, Pastore YD, Thompson AA, Newburger PE, Ravindranath Y, Wang WC, Wlodarski MW, Wang H, Holzhauer S, Breakey VR, Verhovsek M, Kunz J, McNaull MA, Rose MJ, Bradeen HA, Addonizio K, Li A, Al-Sayegh H, London WB, Grace RF. Prevalence and management of iron overload in pyruvate kinase deficiency: report from the Pyruvate Kinase Deficiency Natural History Study. Haematologica. 2019 Feb;104(2):e51-e53. doi: 10.3324/haematol.2018.196295. Epub 2018 Sep 13. No abstract available.
- Background: PubMed 32043619Bianchi P, Fermo E, Lezon-Geyda K, van Beers EJ, Morton HD, Barcellini W, Glader B, Chonat S, Ravindranath Y, Newburger PE, Kollmar N, Despotovic JM, Verhovsek M, Sharma M, Kwiatkowski JL, Kuo KHM, Wlodarski MW, Yaish HM, Holzhauer S, Wang H, Kunz J, Addonizio K, Al-Sayegh H, London WB, Andres O, van Wijk R, Gallagher PG, Grace RFF. Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency. Am J Hematol. 2020 May;95(5):472-482. doi: 10.1002/ajh.25753. Epub 2020 Mar 6.
- Derived from this study: PubMed 34470054Al-Samkari H, van Beers EJ, Morton DH, Eber SW, Chonat S, Kuo KHM, Kollmar N, Wang H, Breakey VR, Sheth S, Sharma M, Forbes PW, Klaassen RJ, Grace RF. Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency. Blood Adv. 2022 Mar 22;6(6):1844-1853. doi: 10.1182/bloodadvances.2021004675.
- Individual participant dataSharing planned: No
Related trials for Pyruvate Kinase Deficiency
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Not Regularly Transfused, Followed by a 5-Year Extension Period
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A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Regularly Transfused, Followed by a 5-Year Extension Period
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A Study to Provide Access to Mitapivat for Participants Who Previously Participated in an Agios-Sponsored Mitapivat Study
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Pyruvate Kinase Deficiency Global Longitudinal Registry
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High-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study
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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.
The record lists no contact. Use the official record to reach the sponsor.
30 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pyruvate Kinase Deficiency and Congenital Non-Spherocytic Hemolytic Anemia, run by Boston Children's Hospital at 30 sites in 6 countries.
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 3 inclusion and 1 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 22 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Germany, Canada, Czechia, Italy and 1 more country. 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?
transfusion burden in splenectomized and non-splenectomized participants (time frame: 12 weeks). 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 NCT02053480, which also lists 4 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 22 May 2020.