Cyanotic Congenital Heart DiseasePhase 2NCT02564796
Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic CHD - A Prospective Control Trial
A Phase 2 study testing Epoetin Alfa and Iron and Iron in people with Cyanotic Congenital Heart Disease and Anemia, run by University of California, San Diego at 1 site in United States.
Trial summary
Cyanotic congenital cardiac patients require higher hemoglobin concentrations (red blood cell levels) for optimal oxygen delivery to the body. Prophylactic erythropoietin (EPO) and iron can prevent and/or decrease the amount of blood transfusions needed in this population. Read more about this study
- Who is it for?
- Ages Up to 8 weeks
- Conditions the study is for
- Cyanotic Congenital Heart Disease, Anemia, Cyanosis
- What is being tested?
- Epoetin Alfa and Iron and Iron
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 8 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Newborns less than 4 weeks old at diagnosis
- Gestational age >34 weeks
- Birth weight 2.2-4kg
- Cyanotic heart disease who have had a surgical shunt or a catheterization intervention that is equivalent to a shunt (patent ductus arteriosus stent, right ventricular outflow tract stent).
- Baseline hematocrit to be below <40%.
- Completes at least 1 injection in the study by 8 weeks of age.
Who cannot join
- Infants diagnosed at greater than 4 weeks of age
- Gestation <34 weeks
- Birth weight <2.2 kg or >4kg
- Hematocrit >40%
- Newborns with acyanotic heart disease
- Infants with significant co-morbidities:
Show all 10Show fewer
- Renal failure (Creatinine > 2 standard deviations above age adjusted norm)
- Hepatic failure (elevated AST/ALT levels > 2 standard deviations above age adjusted norm
- Hemolytic disease
- Hemoglobinopathies (Sickle-cell disease, Thalassemias)
Trial locations and contacts
1 site in 1 country.
United States1 site
Rady Children's Hospital
San Diego, California, 92123
About this study
Official title: Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic Congenital Heart Disease - A Prospective Randomized Control Trial
Cyanotic congenital cardiac patients require higher hemoglobin concentrations (red blood cell levels) for optimal oxygen delivery to the body. Prophylactic erythropoietin (EPO) and iron can prevent and/or decrease the amount of blood transfusions needed in this population. We seek to investigate if EPO and iron make a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it.
Read the detailed description
Congenital heart disease occurs in about 1% of all live births. Cyanotic cardiac lesions in particular are at risk for significant mortality and morbidity because of their reduced ability to provide adequate oxygenation to the body and the brain. Many experts believe that to have adequate oxygen carrying capacity that these infants should ideally have a hemoglobin level greater than 13 g/dL. Many of these patients require blood transfusions prior to surgery to provide adequate oxygenation. The cause for this is likely multifactorial including normal neonatal physiology, frequent lab draws, and co-morbidities. Although rare, the morbidity due to transfusions can be devastating to this population including transmitted infections, transfusion reactions, extra hospitalizations, and antigen sensitization that would complicate heart transplant if needed.
There are centers in the United States that have developed protocols using erythropoietin to minimize blood product transfusions before and after surgery, also referred to as "bloodless surgery". There have been retrospective studies evaluating the success of these protocols, but there are no randomized controlled prospective studies that the investigators have studying the effects of erythropoietin effects in patients with cyanotic heart disease in regards to transfusion prevention.
Congenital cyanotic cardiac patients require higher hemoglobin concentrations for optimal oxygen delivery. Prophylactic erythropoietin can prevent and/or decrease the amount of blood transfusions needed prior to surgery. The researchers seek to investigate if erythropoietin makes a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it.
- Being tested
- Epoetin Alfa and Iron, Iron
- Keywords
- Erythropoetin, Cyanotic Heart Disease, Transfusion, Congenital Heart Disease
- Medical subject headings
- Anemia, Cyanosis, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epoetin Alfa and IronDrug
Also called No other name
Patients in the treatment group will receive weekly EPO injections and iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization) They will be followed for 14 weeks.
IronDrug
Also called No other name
Patients in the treatment group will not receive any extra intervention outside of standard of care. They will receive iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization). They will be followed for 14 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Group II (non-treatment group): Patients in the treatment group will not receive any extra intervention outside of standard of care. They will receive iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization). They will be followed for 14 weeks. Receives: Drug: Iron |
| Epoetin alfa and iron supplements | Experimental | Group I (treatment group): Patients in the treatment group will receive weekly EPO injections and iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization) They will be followed for 14 weeks. Receives: Drug: Epoetin Alfa and Iron |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Transfusions Needed
Prophylactic erythropoietin can prevent and/or decrease the amount of blood transfusions needed prior to surgery. We seek to investigate if erythropoietin makes a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it during the period in which the subjects will be active in the study (from baseline to 14 weeks post initial injection). The primary aim will be assessed when all subjects have completed week 14 or discontinue early.
Measured: First 4 months of life
Secondary outcomes (4)
Oxygen Saturation
Often, cyanotic congenital heart defect neonates have prolonged initial hospital stays due to the inability to maintain acceptable oxygen saturations, and transition to adequate oral intake for appropriate weight gain. If the hospital stay is found to be shortened after starting erythropoietin, this may be of clinical and financial significance.
Measured: First 4 months of life
Number of Hospitalizations
The number of hospital readmissions (related to failure to thrive or cyanosis) may imply the overall clinical stability of a patient. Because these infants are at high risk for mortality at home, there are multiple reasons why they may be admitted to the hospital including clinically significant anemia which requires blood transfusions, poor weight gain, difficulty feeding, inadequate oxygen saturations, and illnesses. Each admission is stressful to the patient and their families. Having a normal hemoglobin level may have a role in preventing several of these factors, especially regarding failure to thrive or cyanosis.
Measured: First 4 months of life
Weight Gain
The secondary outcome of weight gain is appropriate in the setting of infants as this variable has been used to monitor the ability to thrive and meet the body's metabolic demands. It is well established in pediatrics that the neonate and infant should gain 15-30 grams per day for optimal growth. Infants who are cyanotic already have a deficiency in meeting their metabolic demands due to a reduced oxygen carrying capacity. This is further complicated in the instance of anemia. Thus, infants may have an increased ability to optimize weight gain in the setting of normal, stable hemoglobin levels which may be achieved with erythropoietin.
Measured: First 4 months of life
Time to Initial Discharge
If the hospital stay is found to be shortened after starting erythropoietin, this may be of clinical and financial significance.
Measured: First 4 months of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2015 (estimated)
- Study startNov 2016
- Primary completionJun 2020
- Study completionJun 2020
Why it stopped: COVID
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cyanotic Congenital Heart DiseaseStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Werho, MD, University of California, San Diego
- Investigators
- David K Werho, MD, Principal investigator, University of California, San Diego/Rady Children's Hospital San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02564796
- Sponsor's protocol ID
- 160871
- Status last verified
- Nov 2021
- First submitted
- 29 Sep 2015
- Last updated
- 2 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Donato H. Erythropoietin: an update on the therapeutic use in newborn infants and children. Expert Opin Pharmacother. 2005 May;6(5):723-34. doi: 10.1517/14656566.6.5.723.
PubMed 15934899Fearon JA, Weinthal J. The use of recombinant erythropoietin in the reduction of blood transfusion rates in craniosynostosis repair in infants and children. Plast Reconstr Surg. 2002 Jun;109(7):2190-6. doi: 10.1097/00006534-200206000-00002.
PubMed 12045535Maier RF, Obladen M, Muller-Hansen I, Kattner E, Merz U, Arlettaz R, Groneck P, Hammer H, Kossel H, Verellen G, Stock GJ, Lacaze-Masmonteil T, Claris O, Wagner M, Matis J, Gilberg F; European Multicenter Erythropoietin Beta Study Group. Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g. J Pediatr. 2002 Jul;141(1):8-15. doi: 10.1067/mpd.2002.124309.
PubMed 12091844Richard S, Brion JP, Couck AM, Flament-Durand J. Accumulation of smooth endoplasmic reticulum in Alzheimer's disease: new morphological evidence of axoplasmic flow disturbances. J Submicrosc Cytol Pathol. 1989 Jul;21(3):461-7.
PubMed 2477140
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic Congenital Heart Disease - A Prospective Randomized Control Trial
- ClinicalTrials.gov ID
- NCT02564796
- Acronym / sponsor ID
- 160871
- Keywords
- Erythropoetin, Cyanotic Heart Disease, Transfusion, Congenital Heart Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: COVID
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- Jun 2020 (actual)
- Study completion
- Jun 2020 (actual)
- First posted
- 1 Oct 2015 (estimated)
- Results
- Posted 2 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cyanotic congenital cardiac patients require higher hemoglobin concentrations (red blood cell levels) for optimal oxygen delivery to the body. Prophylactic erythropoietin (EPO) and iron can prevent and/or decrease the amount of blood transfusions needed in this population. We seek to investigate if EPO and iron make a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it.
Detailed description
Congenital heart disease occurs in about 1% of all live births. Cyanotic cardiac lesions in particular are at risk for significant mortality and morbidity because of their reduced ability to provide adequate oxygenation to the body and the brain. Many experts believe that to have adequate oxygen carrying capacity that these infants should ideally have a hemoglobin level greater than 13 g/dL. Many of these patients require blood transfusions prior to surgery to provide adequate oxygenation. The cause for this is likely multifactorial including normal neonatal physiology, frequent lab draws, and co-morbidities. Although rare, the morbidity due to transfusions can be devastating to this population including transmitted infections, transfusion reactions, extra hospitalizations, and antigen sensitization that would complicate heart transplant if needed.
There are centers in the United States that have developed protocols using erythropoietin to minimize blood product transfusions before and after surgery, also referred to as "bloodless surgery". There have been retrospective studies evaluating the success of these protocols, but there are no randomized controlled prospective studies that the investigators have studying the effects of erythropoietin effects in patients with cyanotic heart disease in regards to transfusion prevention.
Congenital cyanotic cardiac patients require higher hemoglobin concentrations for optimal oxygen delivery. Prophylactic erythropoietin can prevent and/or decrease the amount of blood transfusions needed prior to surgery. The researchers seek to investigate if erythropoietin makes a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Drug: IronGroup II (non-treatment group): Patients in the treatment group will not receive any extra intervention outside of standard of care. They will receive iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization). They will be followed for 14 weeks. |
| Epoetin alfa and iron supplements | Experimental | Drug: Epoetin Alfa and IronGroup I (treatment group): Patients in the treatment group will receive weekly EPO injections and iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization) They will be followed for 14 weeks. |
Who may qualify
- Ages
- Up to 8 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Newborns less than 4 weeks old at diagnosis
- Gestational age >34 weeks
- Birth weight 2.2-4kg
- Cyanotic heart disease who have had a surgical shunt or a catheterization intervention that is equivalent to a shunt (patent ductus arteriosus stent, right ventricular outflow tract stent).
- Baseline hematocrit to be below <40%.
Key exclusion criteria (10 listed)
- Infants diagnosed at greater than 4 weeks of age
- Gestation <34 weeks
- Birth weight <2.2 kg or >4kg
- Hematocrit >40%
- Newborns with acyanotic heart disease
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 |
|---|---|---|
| Epoetin Alfa and IronAlso: No other namePatients in the treatment group will receive weekly EPO injections and iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization) They will be followed for 14 weeks. | Drug | Epoetin alfa and iron supplements |
| IronAlso: No other namePatients in the treatment group will not receive any extra intervention outside of standard of care. They will receive iron supplementation for 6 weeks starting before 8 weeks of age, 1 week after their first procedure (surgery or heart catheterization). They will be followed for 14 weeks. | Drug | Control |
Primary outcome
Number of Transfusions Needed
Time frame: First 4 months of life
Prophylactic erythropoietin can prevent and/or decrease the amount of blood transfusions needed prior to surgery. We seek to investigate if erythropoietin makes a clinically significant difference in the number of transfusions given to these patients and the morbidity associated with it during the period in which the subjects will be active in the study (from baseline to 14 weeks post initial injection). The primary aim will be assessed when all subjects have completed week 14 or discontinue early.
4 secondary outcomes
Oxygen Saturation
Time frame: First 4 months of life
Number of Hospitalizations
Time frame: First 4 months of life
Weight Gain
Time frame: First 4 months of life
Time to Initial Discharge
Time frame: First 4 months of life
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15934899Donato H. Erythropoietin: an update on the therapeutic use in newborn infants and children. Expert Opin Pharmacother. 2005 May;6(5):723-34. doi: 10.1517/14656566.6.5.723.
- Background: PubMed 12045535Fearon JA, Weinthal J. The use of recombinant erythropoietin in the reduction of blood transfusion rates in craniosynostosis repair in infants and children. Plast Reconstr Surg. 2002 Jun;109(7):2190-6. doi: 10.1097/00006534-200206000-00002.
- Background: PubMed 12091844Maier RF, Obladen M, Muller-Hansen I, Kattner E, Merz U, Arlettaz R, Groneck P, Hammer H, Kossel H, Verellen G, Stock GJ, Lacaze-Masmonteil T, Claris O, Wagner M, Matis J, Gilberg F; European Multicenter Erythropoietin Beta Study Group. Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g. J Pediatr. 2002 Jul;141(1):8-15. doi: 10.1067/mpd.2002.124309.
- Background: PubMed 2477140Richard S, Brion JP, Couck AM, Flament-Durand J. Accumulation of smooth endoplasmic reticulum in Alzheimer's disease: new morphological evidence of axoplasmic flow disturbances. J Submicrosc Cytol Pathol. 1989 Jul;21(3):461-7.
- Individual participant dataSharing planned: No
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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.
David K Werho, MD principal investigator
University of California, San Diego/Rady Children's Hospital San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Epoetin Alfa and Iron and Iron in people with Cyanotic Congenital Heart Disease and Anemia, run by University of California, San Diego at 1 site in United States.
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 6 inclusion and 10 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: stopped early, as of the sponsor's last update on 2 Dec 2021. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Transfusions Needed (time frame: First 4 months of life). 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 NCT02564796, 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 2 Dec 2021.