Retinopathy of PrematurityPhase 2NCT03038295
a Prospective Cohort Study for Propranolol Treatment in Retinopathy of Prematurity
A Phase 2 study testing Propranolol in people with Retinopathy of Prematurity, run by Guangdong Women and Children Hospital.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of oral/local propranolol in preterm newborns who diagnosed as early phase of retinopathy of prematurity (ROP). Read more about this study
- Who is it for?
- Ages Up to 8 weeks
- Conditions the study is for
- Retinopathy of Prematurity
- What is being tested?
- Propranolol
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Mar 2017to Dec 2019
- Phase
- Phase 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 8 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Preterm newborns (birth weight less than 1500g) with stage 1/2 ROP in Zone 2 or 3 without plus
- A signed parental informed consent
Who cannot join
- Newborns with heart failure
- Newborns with recurrent bradycardia (heart rate < 90 beat per minute)
- Newborns with second or third degree atrioventricular block
- Newborns with congenital cardiovascular anomalies, except for persistent ductus arteriosus, patent foramen ovale and small ventricular septal defects
- Newborns with hypotension
- Newborns with renal failure
Show all 9Show fewer
- Newborns with actual cerebral haemorrhage
- Newborns with other diseases which contraindicate the use of beta-adrenoreceptor blockers.
- Newborns with a more severe stage of ROP than stage 2 or in Zone 1
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Safety and Efficacy of Propranolol Treatment in Newborns With Retinopathy of Prematurity:a Prospective Cohort Study
The purpose of this study is to evaluate the safety and efficacy of oral/local propranolol in preterm newborns who diagnosed as early phase of retinopathy of prematurity (ROP).
Read the detailed description
The incidence of Retinopathy of Prematurity (ROP) in preterm newborns less than 1500g is about 60% in the developed countries around the world, while there are much more preterm newborns more than 1500g and 32 weeks gestational age with Retinopathy of Prematurity (ROP) had to be treated in the developing countries. ROP has listed top of the five causes lead to blindness in children, which seriously threated children's vision and quality of life.
The ablation of the retina with photocoagulation by laser or cryotherapy reduces the incidence of blindness by suppressing the neovascular phase of ROP. However, those Surgeries require anesthesia and some of them may result in complications such as apnea, neonatal necrotizing enterocolitis, sepsis, and hemorrhage of digestive tract. As a result, it's important to study an alternative non-surgical treatment method.
The development of ROP depends largely from vascular endothelial growth factor (VEGF). The reduction of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP.
Propranolol is a kind of beta-adrenergic receptor (β-AR) which can inhibit the expression of VEGF and has been first choice of treating infantile hemangioma, the most common tumor of infancy. There are some pilot studies suggesting that the administration of oral propranolol is effective in counteracting the progression of ROP in patients without operation indication. Nevertheless that safety is a concern, for oral propranolol may result in associated complications and side effects such as bradycardia, hypotension, injury of cerebrum growth and olfactory.
Recently a research of eye drop propranolol in a mouse model of oxygen-induced retinopathy (OIR) has shown that propranolol was still effective in inhibiting angiogenic processes, indicating that local administration is equally effective.
The purpose of this study is to evaluate safety and efficacy of oral/local propranolol in preterm newborns with early phase of retinopathy of prematurity (ROP).The study will be followed up for a period of time, observing the development of optic and nerve system complications to further confirm the efficacy of propranolol to ROP treatment, which can provide theoretical basis for the futher clinical application of the drug in ROP.
- Conditions
- Retinopathy of Prematurity
- Being tested
- Propranolol, placebo
- Keywords
- Retinopathy of Prematurity, propranolol, ROP
- Medical subject headings
- Retinopathy of Prematurity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
Oral propranolol:0.25mg/kg daily(every 24 hours)；Eye drop propranolol(0.2%):3 microdrops,in each eye, four times daily (every 6 hours) .Both administration routes will be discontinued until retinal vascularization will be completed, but no more than 90 days.The study will be discontinued immediately in the presence of serious adverse effects attributable to the pharmacological actions of propranolol (severe hypotension, bradycardia or bronchospasm).In case of surgery or induction of anesthesia during the administration of propranolol, the drug should be discontinued at least 24 hours before surgery.In cases of severe hypotension or bradycardia may be administered one or more of the following drugs:Atropine.Isoproterenol hydrochloride (isoprenaline).Terlipressin.Glucagon In case of severe bronchospasm may be used salbutamol aerosol or salbutamol + ipratropium bromide. Betamethasone could be used for aerosol or systemic (intravenous or intramuscular).
placeboDrug
Also called normal saline
Oral/eye drop placebo will be taken in enrolled newborns. Other treatment will follow the standard treatment schedule of Early Treatment For Retinopathy Of Prematurity Cooperative Group.
| Study group | Role | What they receive |
|---|---|---|
| oral propranol group | Experimental | Enrolled preterm newborns will receive oral propranolol 0.25mg/kg daily(every 24 hours).
The treatment will be started as soon as the diagnosis of stage 1 or 2 ROP without plus is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days. Receives: Drug: Propranolol |
| oral placebo group | Placebo comparator | Enrolled preterm newborns will receive oral normal saline 0.25mg/kg daily(every 24 hours) and other disposals will be done similarily to the oral propranol group. Receives: Drug: placebo |
| eye drop propranol group | Experimental | Enrolled preterm newborns will receive propranolol as ophthalmic solution (0.2%). 3 microdrops of 6 microliters (μL) propranolol solution (= 6 μg propranolol/microdrop) will be topically applied with a calibrated pipette,in each eye, four times daily (every 6 hours) .
The treatment will be started as soon as the diagnosis of stage 1 or 2 ROP without plus is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days. Receives: Drug: Propranolol |
| eye drop placebo group | Placebo comparator | Enrolled preterm newborns will receive placebo as ophthalmic solution in the same way of eye drop propranolol and other disposals will be done similarily to the eye drop propranol group. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of newborns who have ROP progression
Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months
Number of newborns who need surgical treatment
Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months
Number of newborns who have side effects
Measured: participants will be followed for the duration of hospital stay, an expected average of 2 months
Plasma concentrations of propranolol at the steady state measured by dried blood spots
Measured: 10th day of treatment
Secondary outcomes (2)
visual assessment of enrolled newborns
Measured: about 12 months
Scores of Gesell development scale of enrolled newborns
Measured: about 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2017 (estimated)
- Study startMar 2017 (estimated)
- Primary completionDec 2018 (estimated)
- Study completionDec 2019 (estimated)
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 Retinopathy of PrematurityStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Women and Children Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nie Chuan, Guangdong Women and Children Hospital
- Investigators
- Chuan Nie, Doctor, Principal investigator, Guangdong Women and Children Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03038295
- Sponsor's protocol ID
- lqiong
- Status last verified
- Feb 2017
- First submitted
- 19 Jan 2017
- Last updated
- 3 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zin A, Gole GA. Retinopathy of prematurity-incidence today. Clin Perinatol. 2013 Jun;40(2):185-200. doi: 10.1016/j.clp.2013.02.001.
PubMed 23719304Fierson WM; American Academy of Pediatrics Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; American Association of Certified Orthoptists. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2013 Jan;131(1):189-95. doi: 10.1542/peds.2012-2996. Epub 2012 Dec 31.
PubMed 23277315Filippi L, Cavallaro G, Bagnoli P, Dal Monte M, Fiorini P, Donzelli G, Tinelli F, Araimo G, Cristofori G, la Marca G, Della Bona ML, La Torre A, Fortunato P, Furlanetto S, Osnaghi S, Mosca F. Oral propranolol for retinopathy of prematurity: risks, safety concerns, and perspectives. J Pediatr. 2013 Dec;163(6):1570-1577.e6. doi: 10.1016/j.jpeds.2013.07.049. Epub 2013 Sep 18.
PubMed 24054431Dal Monte M, Casini G, la Marca G, Isacchi B, Filippi L, Bagnoli P. Eye drop propranolol administration promotes the recovery of oxygen-induced retinopathy in mice. Exp Eye Res. 2013 Jun;111:27-35. doi: 10.1016/j.exer.2013.03.013. Epub 2013 Mar 23.
PubMed 23528535
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Propranolol Treatment in Newborns With Retinopathy of Prematurity:a Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT03038295
- Acronym / sponsor ID
- lqiong
- Conditions
- Retinopathy of Prematurity
- Keywords
- Retinopathy of Prematurity, propranolol, ROP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Guangdong Women and Children HospitalUniversity, hospital or other
- Study start
- Mar 2017 (estimated)
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 31 Jan 2017 (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 evaluate the safety and efficacy of oral/local propranolol in preterm newborns who diagnosed as early phase of retinopathy of prematurity (ROP).
Detailed description
The incidence of Retinopathy of Prematurity (ROP) in preterm newborns less than 1500g is about 60% in the developed countries around the world, while there are much more preterm newborns more than 1500g and 32 weeks gestational age with Retinopathy of Prematurity (ROP) had to be treated in the developing countries. ROP has listed top of the five causes lead to blindness in children, which seriously threated children's vision and quality of life.
The ablation of the retina with photocoagulation by laser or cryotherapy reduces the incidence of blindness by suppressing the neovascular phase of ROP. However, those Surgeries require anesthesia and some of them may result in complications such as apnea, neonatal necrotizing enterocolitis, sepsis, and hemorrhage of digestive tract. As a result, it's important to study an alternative non-surgical treatment method.
The development of ROP depends largely from vascular endothelial growth factor (VEGF). The reduction of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP.
Propranolol is a kind of beta-adrenergic receptor (β-AR) which can inhibit the expression of VEGF and has been first choice of treating infantile hemangioma, the most common tumor of infancy. There are some pilot studies suggesting that the administration of oral propranolol is effective in counteracting the progression of ROP in patients without operation indication. Nevertheless that safety is a concern, for oral propranolol may result in associated complications and side effects such as bradycardia, hypotension, injury of cerebrum growth and olfactory.
Recently a research of eye drop propranolol in a mouse model of oxygen-induced retinopathy (OIR) has shown that propranolol was still effective in inhibiting angiogenic processes, indicating that local administration is equally effective.
The purpose of this study is to evaluate safety and efficacy of oral/local propranolol in preterm newborns with early phase of retinopathy of prematurity (ROP).The study will be followed up for a period of time, observing the development of optic and nerve system complications to further confirm the efficacy of propranolol to ROP treatment, which can provide theoretical basis for the futher clinical application of the drug in ROP.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| oral propranol group | Experimental | Drug: PropranololEnrolled preterm newborns will receive oral propranolol 0.25mg/kg daily(every 24 hours). The treatment will be started as soon as the diagnosis of stage 1 or 2 ROP without plus is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days. |
| oral placebo group | Placebo comparator | Drug: placeboEnrolled preterm newborns will receive oral normal saline 0.25mg/kg daily(every 24 hours) and other disposals will be done similarily to the oral propranol group. |
| eye drop propranol group | Experimental | Drug: PropranololEnrolled preterm newborns will receive propranolol as ophthalmic solution (0.2%). 3 microdrops of 6 microliters (μL) propranolol solution (= 6 μg propranolol/microdrop) will be topically applied with a calibrated pipette,in each eye, four times daily (every 6 hours) . The treatment will be started as soon as the diagnosis of stage 1 or 2 ROP without plus is made and will be continue until the development of retinal vascularization is completed, but no more than 90 days. |
| eye drop placebo group | Placebo comparator | Drug: placeboEnrolled preterm newborns will receive placebo as ophthalmic solution in the same way of eye drop propranolol and other disposals will be done similarily to the eye drop propranol group. |
Who may qualify
- Ages
- Up to 8 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Preterm newborns (birth weight less than 1500g) with stage 1/2 ROP in Zone 2 or 3 without plus
- A signed parental informed consent
Key exclusion criteria (9 listed)
- Newborns with heart failure
- Newborns with recurrent bradycardia (heart rate < 90 beat per minute)
- Newborns with second or third degree atrioventricular block
- Newborns with congenital cardiovascular anomalies, except for persistent ductus arteriosus, patent foramen ovale and small ventricular septal defects
- Newborns with hypotension
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 |
|---|---|---|
| PropranololOral propranolol:0.25mg/kg daily(every 24 hours)；Eye drop propranolol(0.2%):3 microdrops,in each eye, four times daily (every 6 hours) .Both administration routes will be discontinued until retinal vascularization will be completed, but no more than 90 days.The study will be discontinued immediately in the presence of serious adverse effects attributable to the pharmacological actions of propranolol (severe hypotension, bradycardia or bronchospasm).In case of surgery or induction of anesthesia during the administration of propranolol, the drug should be discontinued at least 24 hours before surgery.In cases of severe hypotension or bradycardia may be administered one or more of the following drugs:Atropine.Isoproterenol hydrochloride (isoprenaline).Terlipressin.Glucagon In case of severe bronchospasm may be used salbutamol aerosol or salbutamol + ipratropium bromide. Betamethasone could be used for aerosol or systemic (intravenous or intramuscular). | Drug | eye drop propranol group, oral propranol group |
| placeboAlso: normal salineOral/eye drop placebo will be taken in enrolled newborns. Other treatment will follow the standard treatment schedule of Early Treatment For Retinopathy Of Prematurity Cooperative Group. | Drug | eye drop placebo group, oral placebo group |
Primary outcome
Number of newborns who have ROP progression
Time frame: participants will be followed for the duration of hospital stay, an expected average of 2 months
Number of newborns who need surgical treatment
Time frame: participants will be followed for the duration of hospital stay, an expected average of 2 months
Number of newborns who have side effects
Time frame: participants will be followed for the duration of hospital stay, an expected average of 2 months
Plasma concentrations of propranolol at the steady state measured by dried blood spots
Time frame: 10th day of treatment
2 secondary outcomes
visual assessment of enrolled newborns
Time frame: about 12 months
Scores of Gesell development scale of enrolled newborns
Time frame: about 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2017.
- Background: PubMed 23719304Zin A, Gole GA. Retinopathy of prematurity-incidence today. Clin Perinatol. 2013 Jun;40(2):185-200. doi: 10.1016/j.clp.2013.02.001.
- Background: PubMed 23277315Fierson WM; American Academy of Pediatrics Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; American Association of Certified Orthoptists. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2013 Jan;131(1):189-95. doi: 10.1542/peds.2012-2996. Epub 2012 Dec 31.
- Background: PubMed 24054431Filippi L, Cavallaro G, Bagnoli P, Dal Monte M, Fiorini P, Donzelli G, Tinelli F, Araimo G, Cristofori G, la Marca G, Della Bona ML, La Torre A, Fortunato P, Furlanetto S, Osnaghi S, Mosca F. Oral propranolol for retinopathy of prematurity: risks, safety concerns, and perspectives. J Pediatr. 2013 Dec;163(6):1570-1577.e6. doi: 10.1016/j.jpeds.2013.07.049. Epub 2013 Sep 18.
- Background: PubMed 23528535Dal Monte M, Casini G, la Marca G, Isacchi B, Filippi L, Bagnoli P. Eye drop propranolol administration promotes the recovery of oxygen-induced retinopathy in mice. Exp Eye Res. 2013 Jun;111:27-35. doi: 10.1016/j.exer.2013.03.013. Epub 2013 Mar 23.
- Drug InformationLink provided by the sponsor.
- 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.
Chuan Nie, Doctor principal investigator
Guangdong Women and Children Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Propranolol in people with Retinopathy of Prematurity, run by Guangdong Women and Children Hospital.
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 2 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 3 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chuan Nie, Doctor (+86-136-8227-0294, chuannie@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of newborns who have ROP progression (time frame: participants will be followed for the duration of hospital stay, an expected average of 2 months). The study lists 4 primary outcomes in all. 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 NCT03038295, 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 3 Feb 2017.