Trial Outcomes & Findings for A Randomized Trial of Low-Dose Bevacizumab vs Laser for Type 1 ROP (NCT NCT04634604)

Last Updated: 2024-08-01

Results Overview

The primary objective for the randomized trial is to determine if infants with type 1 ROP treated with intravitreal bevacizumab (subsequently referred to as BV) have a treatment success rate determined at 6 months adjusted age that is non-inferior compared with infants treated with laser photocoagulation (subsequently referred to as LASER).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

16 participants

Primary outcome timeframe

6 Months Adjusted Age

Results posted on

2024-08-01

Participant Flow

Participant milestones

Participant milestones
Measure	Laser For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by Occupational Safety and Health Administration (OSHA) and facility standards, will be followed. Laser: For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by OSHA and facility standards, will be followed.	Bevacizumab For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated. Bevacizumab: For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated.
Overall Study STARTED	9	7
Overall Study COMPLETED	9	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized Trial of Low-Dose Bevacizumab vs Laser for Type 1 ROP

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab n=7 Participants For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated. Bevacizumab: For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated.	Laser n=9 Participants For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by Occupational Safety and Health Administration (OSHA) and facility standards, will be followed. Laser: For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by OSHA and facility standards, will be followed.	Total n=16 Participants Total of all reporting groups
Age, Continuous	25 weeks STANDARD_DEVIATION 1 • n=5 Participants	24 weeks STANDARD_DEVIATION 1 • n=7 Participants	24 weeks STANDARD_DEVIATION 1 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Birth Weight	698 grams STANDARD_DEVIATION 122 • n=5 Participants	670 grams STANDARD_DEVIATION 141 • n=7 Participants	682 grams STANDARD_DEVIATION 129 • n=5 Participants

PRIMARY outcome

Timeframe: 6 Months Adjusted Age

Population: Study terminated due to lack of feasibility of recruitment. No analyses conducted due to lack of power for analysis given small sample size.

Outcome measures

Outcome measures
Measure	Bevacizumab n=3 Participants For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated. Bevacizumab: For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated.	Laser n=5 Participants For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by Occupational Safety and Health Administration (OSHA) and facility standards, will be followed. Laser: For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by OSHA and facility standards, will be followed.
Treatment Success Rate At 6 Months Adjusted Age	3 Participants	4 Participants

Adverse Events

Bevacizumab

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Laser

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab n=7 participants at risk For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated. Bevacizumab: For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated.	Laser n=9 participants at risk For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by Occupational Safety and Health Administration (OSHA) and facility standards, will be followed. Laser: For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by OSHA and facility standards, will be followed.
Ear and labyrinth disorders Eustachian tube dysfunction	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Infections and infestations Viral Syndrome	14.3% 1/7 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Injury, poisoning and procedural complications Head Injury	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Metabolism and nutrition disorders Failure to Thrive	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Nervous system disorders Cerebral Palsy	14.3% 1/7 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Nervous system disorders Hydrocephalus	14.3% 1/7 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Respiratory, thoracic and mediastinal disorders Primary Apnea of premature newborns	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	22.2% 2/9 • Number of events 2 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Respiratory, thoracic and mediastinal disorders Respiratory infection	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Reproductive system and breast disorders Respiratory insufficiency	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).

Other adverse events

Additional Information

Ray Kraker

Jaeb Center for Health Research

Phone: 8139758690

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Bevacizumab n=7 participants at risk For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated. Bevacizumab: For infants randomized to bevacizumab, the Intravitreous bevacizumab 0.063 mg injection will be given no later than 2 days after the diagnosis of type 1 ROP. The ophthalmologist may choose to give the intravitreous injection in the operating room or at the bedside, with or without anesthesia, after consultation with the attending neonatologist. A binocular indirect ophthalmoscope with an appropriate condensing lens should be available, and the pupils should be dilated.	Laser n=9 participants at risk For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by Occupational Safety and Health Administration (OSHA) and facility standards, will be followed. Laser: For infants randomized to laser treatment, it will be given in conjunction with a binocular indirect ophthalmoscope and an appropriate condensing lens, by a study-certified ophthalmologist experienced in the use of this equipment. The treating investigator will be certified as having sufficient experience with laser for ROP, and adequacy of laser treatment will be confirmed by expert review of photographs. Special laser precautions, as mandated by OSHA and facility standards, will be followed.
Eye disorders Corneal edema	14.3% 1/7 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Eye disorders Esotropia	14.3% 1/7 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Eye disorders Myopia	14.3% 1/7 • Number of events 2 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Eye disorders Preretinal Hemorrhage	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	22.2% 2/9 • Number of events 3 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Eye disorders Retinal Hemorrhage	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Cardiac disorders Bradycardia	28.6% 2/7 • Number of events 2 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Cardiac disorders Cardiac Arrhythmia	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Gastrointestinal disorders Bloody stool	14.3% 1/7 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
General disorders Electrolyte and fluid balance condition	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Infections and infestations COVID-19	14.3% 1/7 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Infections and infestations Streptococcal infection NOS	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Infections and infestations Thrush	14.3% 1/7 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Infections and infestations Viral Syndrome	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Investigations Oxygen Saturations Low	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Musculoskeletal and connective tissue disorders Fractured Ribs	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Musculoskeletal and connective tissue disorders Osteopenia	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Nervous system disorders Neurologic disorder NOS	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Respiratory, thoracic and mediastinal disorders Primary apnea of premature newborns	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Respiratory, thoracic and mediastinal disorders Tachypnea	14.3% 1/7 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	0.00% 0/9 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).
Skin and subcutaneous tissue disorders Skin Abrasion	0.00% 0/7 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).	11.1% 1/9 • Number of events 1 • Adverse events were collected throughout the study until study completion, up to 1 year (terminated early).