Hypoplastic Left HeartPhase 1/2NCT04090697
Use of Oxandrolone to Promote Growth in Infants With HLHS
A Phase 1/2 study testing Oxandrolone in people with Hypoplastic Left Heart and Congenital Heart Disease, run by Carelon Research at 10 sites in 2 countries.
Trial summary
The primary aim of this study is to determine if clinically relevant doses of buccally administered oxandrolone are safe and tolerable in neonates with hypoplastic left heart syndrome (HLHS) or other single right ventricular anomalies who have undergone a Norwood procedure. Read more about this study
- Who is it for?
- Ages Up to 14 days
- Conditions the study is for
- Hypoplastic Left Heart, Congenital Heart Disease
- What is being tested?
- Oxandrolone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 20 Dec 2019to 19 Sep 2023
- Phase
- Phase 1/2
- 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 Up to 14 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- HLHS and other single ventricle of right ventricular morphology
- Age and Norwood procedure ≤14 days of age
- Informed consent from parent/guardian
Who cannot join
- Small for gestational age (birth weight <10th percentile for gestational age)
- Prematurity, defined as gestational age <37 weeks
- Intrauterine growth retardation (birth weight ≤2.5 kg and gestational age ≥38 weeks)
- Chromosomal abnormality, recognizable genetic syndrome or congenital anomalies of more than minor severity associated with growth failure
- Moderate or greater right ventricular systolic dysfunction and/or moderate or greater tricuspid regurgitation prior to the Norwood procedure
- Extracorporeal membrane oxygenation support (ECMO) prior to or within 24 hours of Norwood procedure
Show all 16Show fewer
- Pre-Norwood interventions (fetal intervention, balloon atrial septostomy for an intact or restrictive atrial septum)
- Pre-Norwood pulmonary venous obstruction
- Pre-Norwood procedure necrotizing enterocolitis and/or other gastrointestinal syndromes
- Known contraindication to oxandrolone
- Planned or current warfarin therapy at screening (warfarin effects are increased by anabolic drugs)
- Significant hepatic dysfunction (elevation of serum transaminase levels greater than two times the upper limit of normal local laboratory standard at screening)
- Hypercalcemia (>1.5 times upper normal range for lab)
- Nephrotic syndrome
- Unwillingness or inability to return to surgical center for follow-up evaluation
- Participation in another clinical study that may impact growth
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
University of Michigan Health System, Ann Arbor
Ann Arbor, Michigan, 48109
Children's Hospital of Atlanta
Atlanta, Georgia, 30322
Boston Children's Hospital
Boston, Massachusetts, 02115
Medical University of South Carolina
Charleston, South Carolina, 29425
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Cook Children's Medical Center
Fort Worth, Texas, 76104
Texas Children's Hospital
Houston, Texas, 77030
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Primary Children's Medical Center
Salt Lake City, Utah, 84113
About this study
Official title: Use of Oxandrolone to Promote Growth in Infants With Hypoplastic Left Heart Syndrome: A Phase I/II Pilot Study
The primary aim of this study is to determine if clinically relevant doses of buccally administered oxandrolone are safe and tolerable in neonates with hypoplastic left heart syndrome (HLHS) or other single right ventricular anomalies who have undergone a Norwood procedure. The secondary aim is to evaluate the efficacy of buccally administered oxandrolone in improving objective indices of growth and nutrition in neonates who have undergone a Norwood procedure.
Read the detailed description
The proposed investigation is a Phase I/II randomized trial of 28 days of open label oxandrolone vs. no oxandrolone treatment to assess optimal dosing, safety/tolerability, and preliminary efficacy of this therapy in post-Norwood neonates with HLHS. Control subjects will receive standard therapy with no placebo and no oxandrolone.
This trial is aimed at cumulative dose finding as well as a preliminary assessment of safety/tolerability and efficacy. The design and dosing are based upon preliminary phase I data obtained as part of an ongoing protocol under IND #107706. This trial will initially include two arms (control and 0.1 mg/kg oxandrolone BID). This initial oxandrolone dose was chosen based on the preliminary data collected in the background studies conducted for this trial. There were no adverse safety outcomes in the small cohort of subjects receiving 0.1 mg/kg of oxandrolone BID.
In Cohort 1, subjects will be block randomized into each arm in a 1:4 (control to oxandrolone) ratio. An interim analysis of the safety data will be performed after the first 25 subjects in Cohort 1 have been randomized and have completed 28 days of oxandrolone therapy or observation (control group). If there are no significant differences in the primary safely/tolerability outcome and safety reviews are favorable for BID dosing, then Cohort 2 (25 subjects) will be randomized in a 1:4 ratio to the control and TID dosing arms. A similar interim analysis will be performed after Cohort 2 subjects have been randomized and completed 28 days of oxandrolone therapy. Enrollment will again be suspended during this second interim analysis to determine if dose escalation is warranted. Cohort 3A, utilizing 0.15 mg/kg oxandrolone TID would be possible if both Cohorts 1 (0.1 mg/kg BID) and 2 (0.1 mg/kg/dose TID) do not demonstrate any differences in the primary safety/tolerability outcome compared to controls and safety reviews are favorable (Figure 4). If the safety threshold is crossed, then a dose of 0.1 mg/kg/dose BID will be used for cohort 3B. An interim safety analysis will be performed after 25 subjects have been enrolled in this highest dosing arm. If at any point a risk-benefit balance in any cohort is found to be negative, then further enrollment will proceed at the lower dosing arm determined to be safe/tolerable based on the primary outcome and safety review with a 1:4 control:oxandrolone ratio and a total subject number of 100.
If the second interim safety analysis leads to the conclusion that the lower dose (0.1 mg/kg oxandrolone BID) appears to be safe and well tolerated, while the higher dose (0.1 mg/kg oxandrolone TID) is not, then the enrollment will proceed in the 0.1 mg/kg BID arm with a 1:4 ratio. If the lowest dose of oxandrolone (0.1 mg/kg BID) is found to be unsafe, then the trial will be stopped. The benefit of this approach lies in the ability to allocate patients to the highest safe dose arm thus enriching the relevance of safety/tolerability and efficacy information obtained. A higher-dose treatment arm will be used if the data reveal the initial treatment arm is not different from control with regards to the primary outcome. If no safety/tolerability effect is demonstrated, the trial will, by design, function as a randomized, controlled trial with dose-escalation. It is anticipated that the study will conclude with approximately 80 oxandrolone patients (in up to three dosing arms) and 20 control patients.
- Conditions
- Hypoplastic Left Heart, Congenital Heart Disease
- Being tested
- Oxandrolone
- Medical subject headings
- Hypoplastic Left Heart Syndrome, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxandroloneDrug
Also called Anavar, Oxandrin
Oxandrolone 2.5mg tabs will be suspended in multi-chain triglyceride (MCT) oil and administered buccally.
| Study group | Role | What they receive |
|---|---|---|
| Oxandrolone Cohort 1 | Experimental | Participants randomized to Oxandrolone Cohort 1 will receive 0.1mg/kg of oxandrolone suspended in a multi-chain triglyceride (MCT) oil buccally twice per day. Receives: Drug: Oxandrolone |
| Standard of Care | No intervention | Participants randomized to standard of care will receive the standard therapies provided at the institution at which they are being treated. Control subjects will receive standard therapy with no placebo and no oxandrolone. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biochemical evidence of hepatic dysfunction
Elevation of serum transaminase levels (alanine transaminase (ALT) and/or aspartate transaminase (AST)) >4 times the local laboratory upper limit of normal
Measured: From date of treatment initiation until the pre-SCPC evaluation or end of study participation, whichever comes first, up to 9 months
Virilization
Standardized physical examination will be performed. Because there are no standard normal values for the various measurements included, each subject will serve as their own control
Measured: From date of treatment initiation until the completion of study drug therapy or end of study participation, whichever comes first, up to 28 days
SAE probably or definitely related to oxandrolone therapy
Any SAE probably or definitely related to oxandrolone therapy in the opinion of the medical monitor
Measured: From date of treatment initiation until the pre-SCPC evaluation or end of study participation, whichever comes first, up to 9 months
Secondary outcomes (7)
Length-for-age z-score
The efficacy of buccally administered oxandrolone will be evaluated by measuring length-for-age z-score at the end of study drug therapy
Measured: At the time of completion of study drug therapy, up to 28 days after date of treatment initiation
Weight-for-age z-score
The efficacy of buccally administered oxandrolone will be evaluated by measuring weight-for-age z-score at the end of study drug therapy
Measured: At the time of completion of study drug therapy, up to 28 days after date of treatment initiation
Change in Weight-for-age z-score
The efficacy of buccally administered oxandrolone will be evaluated by measuring the change in weight-for-age z-score at the end of study drug therapy
Measured: From date of pre-Norwood procedure until completion of study drug therapy, up to 28 days
Change in length-for-age z-score
The efficacy of buccally administered oxandrolone will be evaluated by measuring the change in length-for-age z-score at the end of study drug therapy
Measured: From date of pre-Norwood procedure until completion of study drug therapy, up to 28 days
Prealbumin levels
Serum prealbumin levels will be measured weekly
Measured: During the duration of therapy
Lean Body Mass
Lean body mass will be assessed using dual energy x-ray absorptiometry (DXA)
Measured: At the completion of study drug therapy, assessed up to 35 days after initiation of study drug therapy
Decreased right ventricular systolic function
Evidence of ≥moderate right ventricular systolic dysfunction or tricuspid valve regurgitation based on qualitative assessment of clinical echocardiograms if performed
Measured: At the time of Norwood discharge and at the time of pre-SCPC evaluation, up to 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2019
- Study start20 Dec 2019
- Primary completion19 Sep 2023
- Study completion19 Sep 2023
Why it stopped: FDA withdrawal of Oxandrin NDA and generic ANDAs
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypoplastic Left HeartStudies 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 1/2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carelon Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Phillip T Burch, MD, Principal investigator, University of Mississippi Medical CenterRichard V Williams, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04090697
- Sponsor's protocol ID
- Oxandrolone
- Status last verified
- Jul 2023
- First submitted
- 4 Apr 2019
- Last updated
- 23 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Oxandrolone to Promote Growth in Infants With Hypoplastic Left Heart Syndrome: A Phase I/II Pilot Study
- ClinicalTrials.gov ID
- NCT04090697
- Acronym / sponsor ID
- Oxandrolone
- Conditions
- Hypoplastic Left Heart, Congenital Heart Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: FDA withdrawal of Oxandrin NDA and generic ANDAs
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Carelon ResearchUniversity, hospital or other
- Study start
- 20 Dec 2019 (actual)
- Primary completion
- 19 Sep 2023 (actual)
- Study completion
- 19 Sep 2023 (actual)
- First posted
- 16 Sep 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.
The primary aim of this study is to determine if clinically relevant doses of buccally administered oxandrolone are safe and tolerable in neonates with hypoplastic left heart syndrome (HLHS) or other single right ventricular anomalies who have undergone a Norwood procedure. The secondary aim is to evaluate the efficacy of buccally administered oxandrolone in improving objective indices of growth and nutrition in neonates who have undergone a Norwood procedure.
Detailed description
The proposed investigation is a Phase I/II randomized trial of 28 days of open label oxandrolone vs. no oxandrolone treatment to assess optimal dosing, safety/tolerability, and preliminary efficacy of this therapy in post-Norwood neonates with HLHS. Control subjects will receive standard therapy with no placebo and no oxandrolone.
This trial is aimed at cumulative dose finding as well as a preliminary assessment of safety/tolerability and efficacy. The design and dosing are based upon preliminary phase I data obtained as part of an ongoing protocol under IND #107706. This trial will initially include two arms (control and 0.1 mg/kg oxandrolone BID). This initial oxandrolone dose was chosen based on the preliminary data collected in the background studies conducted for this trial. There were no adverse safety outcomes in the small cohort of subjects receiving 0.1 mg/kg of oxandrolone BID.
In Cohort 1, subjects will be block randomized into each arm in a 1:4 (control to oxandrolone) ratio. An interim analysis of the safety data will be performed after the first 25 subjects in Cohort 1 have been randomized and have completed 28 days of oxandrolone therapy or observation (control group). If there are no significant differences in the primary safely/tolerability outcome and safety reviews are favorable for BID dosing, then Cohort 2 (25 subjects) will be randomized in a 1:4 ratio to the control and TID dosing arms. A similar interim analysis will be performed after Cohort 2 subjects have been randomized and completed 28 days of oxandrolone therapy. Enrollment will again be suspended during this second interim analysis to determine if dose escalation is warranted. Cohort 3A, utilizing 0.15 mg/kg oxandrolone TID would be possible if both Cohorts 1 (0.1 mg/kg BID) and 2 (0.1 mg/kg/dose TID) do not demonstrate any differences in the primary safety/tolerability outcome compared to controls and safety reviews are favorable (Figure 4). If the safety threshold is crossed, then a dose of 0.1 mg/kg/dose BID will be used for cohort 3B. An interim safety analysis will be performed after 25 subjects have been enrolled in this highest dosing arm. If at any point a risk-benefit balance in any cohort is found to be negative, then further enrollment will proceed at the lower dosing arm determined to be safe/tolerable based on the primary outcome and safety review with a 1:4 control:oxandrolone ratio and a total subject number of 100.
If the second interim safety analysis leads to the conclusion that the lower dose (0.1 mg/kg oxandrolone BID) appears to be safe and well tolerated, while the higher dose (0.1 mg/kg oxandrolone TID) is not, then the enrollment will proceed in the 0.1 mg/kg BID arm with a 1:4 ratio. If the lowest dose of oxandrolone (0.1 mg/kg BID) is found to be unsafe, then the trial will be stopped. The benefit of this approach lies in the ability to allocate patients to the highest safe dose arm thus enriching the relevance of safety/tolerability and efficacy information obtained. A higher-dose treatment arm will be used if the data reveal the initial treatment arm is not different from control with regards to the primary outcome. If no safety/tolerability effect is demonstrated, the trial will, by design, function as a randomized, controlled trial with dose-escalation. It is anticipated that the study will conclude with approximately 80 oxandrolone patients (in up to three dosing arms) and 20 control patients.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oxandrolone Cohort 1 | Experimental | Drug: OxandroloneParticipants randomized to Oxandrolone Cohort 1 will receive 0.1mg/kg of oxandrolone suspended in a multi-chain triglyceride (MCT) oil buccally twice per day. |
| Standard of Care | No intervention | –Participants randomized to standard of care will receive the standard therapies provided at the institution at which they are being treated. Control subjects will receive standard therapy with no placebo and no oxandrolone. |
Who may qualify
- Ages
- Up to 14 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- HLHS and other single ventricle of right ventricular morphology
- Age and Norwood procedure ≤14 days of age
- Informed consent from parent/guardian
Key exclusion criteria (16 listed)
- Small for gestational age (birth weight <10th percentile for gestational age)
- Prematurity, defined as gestational age <37 weeks
- Intrauterine growth retardation (birth weight ≤2.5 kg and gestational age ≥38 weeks)
- Chromosomal abnormality, recognizable genetic syndrome or congenital anomalies of more than minor severity associated with growth failure
- Moderate or greater right ventricular systolic dysfunction and/or moderate or greater tricuspid regurgitation prior to the Norwood procedure
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 |
|---|---|---|
| OxandroloneAlso: Anavar, OxandrinOxandrolone 2.5mg tabs will be suspended in multi-chain triglyceride (MCT) oil and administered buccally. | Drug | Oxandrolone Cohort 1 |
Primary outcome
Biochemical evidence of hepatic dysfunction
Time frame: From date of treatment initiation until the pre-SCPC evaluation or end of study participation, whichever comes first, up to 9 months
Elevation of serum transaminase levels (alanine transaminase (ALT) and/or aspartate transaminase (AST)) >4 times the local laboratory upper limit of normal
Virilization
Time frame: From date of treatment initiation until the completion of study drug therapy or end of study participation, whichever comes first, up to 28 days
Standardized physical examination will be performed. Because there are no standard normal values for the various measurements included, each subject will serve as their own control
SAE probably or definitely related to oxandrolone therapy
Time frame: From date of treatment initiation until the pre-SCPC evaluation or end of study participation, whichever comes first, up to 9 months
Any SAE probably or definitely related to oxandrolone therapy in the opinion of the medical monitor
7 secondary outcomes
Length-for-age z-score
Time frame: At the time of completion of study drug therapy, up to 28 days after date of treatment initiation
Weight-for-age z-score
Time frame: At the time of completion of study drug therapy, up to 28 days after date of treatment initiation
Change in Weight-for-age z-score
Time frame: From date of pre-Norwood procedure until completion of study drug therapy, up to 28 days
Change in length-for-age z-score
Time frame: From date of pre-Norwood procedure until completion of study drug therapy, up to 28 days
Prealbumin levels
Time frame: During the duration of therapy
Lean Body Mass
Time frame: At the completion of study drug therapy, assessed up to 35 days after initiation of study drug therapy
Decreased right ventricular systolic function
Time frame: At the time of Norwood discharge and at the time of pre-SCPC evaluation, up to 9 months
Results and safety
The study was stopped early (reason given: FDA withdrawal of Oxandrin NDA and generic ANDAs). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2024.
- 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.
Phillip T Burch, MD principal investigator
University of Mississippi Medical Center
Richard V Williams, MD principal investigator
University of Utah
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Oxandrolone in people with Hypoplastic Left Heart and Congenital Heart Disease, run by Carelon Research at 10 sites in 2 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 16 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 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Canada. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was stopped early (reason given: FDA withdrawal of Oxandrin NDA and generic ANDAs). Results are not available in the source record.
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?
Biochemical evidence of hepatic dysfunction (time frame: From date of treatment initiation until the pre-SCPC evaluation or end of study participation, whichever comes first, up to 9 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 May 2024; AzTrials last refreshed its copy on 8 Nov 2026.