Air Tamponade Versus Fluorinated Gas Tamponade for Rhegmatogenous Retinal Detachment
- Conditions
- Retinal Detachment Rhegmatogenous
- Registration Number
- NCT07034469
- Brief Summary
TITLE: RCT of air tamponade versus fluorinated gas tamponade for rhegmatogenous retinal detachment DESIGN: Non-inferiority RCT of 150 patients from 10 UK centres AIMS: To assess whether air tamponade is non inferior to gas tamponade for the repair of RRD treated with vitrectomy.
PRIMARY OUTCOME MEASURE: Primary anatomical success with single operation at 24 weeks.
BACKGROUND Rhegmatogenous retinal detachment (RRD) is the most common form of RD developing when there is a retinal 'break' that allows the ingress of fluid from the vitreous cavity into the subretinal space. There are three main current options for the management of RRD, namely pneumoretinopexy, scleral buckling and vitrectomy (PPV). Vitrectomy is currently performed for the majority of RRDs in the UK. Tamponade in PPV is usually performed by complete filling of the vitreous cavity with fluorinated gases diluted in air at iso-volumetric concentrations which do not expand (e.g., 20% SF6 or 14% C3F8).
RATIONALE FOR CURRENT STUDY The use of air instead of fluorinated gases in primary RRD treated with vitrectomy has been the subject of much debate recently. Air being non expansile and short lived it offers the prospect of quicker rehabilitation and less risk and avoids the use of environmentally damaging fluorinated gases. The question of whether air offers equivalence to gas for uncomplicated RRD with mainly superior breaks has not been adequately answered, as reviewed in a recent systematic review and meta-analysis where the certainty of evidence was judged very low. This type of detachment is the commonest at approximately 60% of the cases in the BEAVRS database and representing approximately 4,800 RRD in the UK per annum. There has been significant interest in air recently with the announcement of the European chemical agencies proposed ban on fluorinated gases.
There are several potential benefits of using air over gas to repair detached retinas.
1. Speedier visual recovery, which may mean earlier return to work or normal activities.
2. Avoiding expansile fluorinated gas-related complications such as raised eye pressure, reducing the number of post-operative visits and medications needed after surgery.
3. Fewer restrictions after surgery (able to fly and drive sooner and shorter restrictions on anaesthetic agents)
4. Decreased environmental impact by reducing greenhouse gas use. If air was proven to be non-inferior to gas, then patients with RRD treated by vitrectomy would likely prefer it
- Detailed Description
STUDY OBJECTIVES To assess whether air tamponade is non inferior to gas tamponade for the repair of RRD with superior breaks treated with vitrectomy and to assess how cost-effective air tamponade is compared to gas tamponade STUDY DESIGN RCT of people presenting with uncomplicated RRD treated with vitrectomy comparing air to gas tamponade.
Participants will be randomised 1:1 between air tamponade and gas tamponade. Randomisation will be performed using a secure web-based randomisation system at the time of surgery.
STUDY OUTCOME MEASURES Primary outcome measure: Primary anatomical success with single operation at 6 months Secondary outcomes: Postoperative VA at 10 days, 6 and 24 weeks. PARTICIPANT ENTRY
1. INCLUSION CRITERIA Primary uncomplicated RRD undergoing vitrectomy. Phakic and pseudophakic eyes Retinal breaks superiorly between 3 and 9 o'clock, and that are separated by less than 4 clock hours.
Exclusion:
Absence of PVD Age 40 years or younger PVR grade C or above Aphakia or anterior chamber lens Retinal breaks greater than 1 clock hour in size Retinal breaks that exist below 3 and 9 o'clock on both the nasal and temporal sides. Retinal breaks at or posterior to the vessel arcades Current or previous -6D myopia or greater (or axial length \>26millimetres (mm)) Chronic RRD judged by the presence of subretinal bands and other signs of chronicity or by history of visual loss for \>28 days. Significant inflammation, choroidal detachments, hypotony (\<6 millimetres of mercury (mmHg) preop) Previous open-globe injury, or endophthalmitis Current or previous posterior uveitis or choroiditis Any intraocular surgical procedure within 4 weeks other than laser/cryotherapy Any other condition that, in the opinion of the investigator, would prevent the participant from granting informed consent or complying with the protocol.
2. PARTICIPANT CONSENT PROCESS Potentially eligible patients with capacity to consent will have the standard surgical pathway and trial options described in detail. Written trial participant information sheets will be provided with font size as required. Patients will be given time to read the material, ask questions, and consider the options. This period will typically be a few days or up to a week.
The study participant information sheet (PIS) will be provided in English, but a hospital interpreting service will be made available for non-English speaking patients. Children and vulnerable populations will not be recruited to this study.
A copy of the informed consent will be kept in the participant's medical notes/uploaded in electronic case records to underscore their participation in GREEN. The participant's General Practitioner (GP) will be informed that they have entered the trial (if the participant consents to this).
STUDY INTERVENTION Randomisation will occur at the time of surgery by a research nurse, when the surgeon is satisfied that the patient is eligible which will be during the surgery to ensure all breaks are identified correctly.
Participants will be randomised 1:1 between air tamponade and gas tamponade. Randomisation will be performed using a secure web-based randomisation system.
All patients will undergo vitrectomy and laser-retinopexy as per SOC. Phaco-vitrectomy will be allowed as per surgeon practice.Patients randomised to standard surgery will have gas tamponade as per their own standard choice and carried out as per the surgeon's standard technique. Retinopexy will be undertaken with endolaser.
Patients randomised to air, will have air tamponade. Both groups will be postured face down for 4 hours postoperatively immediately upon the completion of surgery then based on breaks as per surgeon instructions for 7 days as per SOC ADVERSE EVENTS
1. REPORTING PROCEDURES All serious adverse events (SAEs) will be recorded in the medical records and the CRF.
All SAEs must be recorded on a serious adverse event (SAE) form. The PI or designated individual will complete an SAE form and it should be emailed to both the R\&D team of the Liverpool University Hospitals NHS Foundation Trust and to the Chief Investigator within 1 working day of becoming aware of the event.
Where the event is unexpected and thought to be related to the procedure this must be reported by the Investigator to the REC and Health Research Authority, using the SAE Report form for non-CTIMPs (available from the HRA website) within 15 days.
All reporting to Liverpool University Hospitals NHS Foundation Trust should be by e-mail giving as much information about the incident as possible and should be signed by the PI or Co-investigator.
The Sponsor will undertake an initial review of the information. Events will be followed up until resolution, and any appropriate further information will be sent by the research team in a timely manner.
Non serious AEs All Adverse events will be recorded in the CRF following consent until the patient completes the study.
For adverse event reporting, the CORDS classification will be used. Minor complications, scored 1 and 2, will not need to be reported. Intraocular pressure elevation to less than 25 mmHg on the day 1 or week 1-2 post-operative visit does not need to be recorded as an AE or SAE, as this is common after vitrectomy, but the use of any pressuring lowering medicines should be recorded on the CRF.
New retinal breaks and lens touch that occur during surgery do not need to be recorded as an AE or SAE but recorded on the operation notes.
ASSESSMENT AND FOLLOW-UP
Visit schedule:
Preop (within 24 hours of surgery) Surgery Day 1 10 days postop (+/- 3 days) 6 weeks postop (+/-1 week) 6 months post op (+/-2 weeks)
Visits will include:
Consent Randomisation Visual acuity - BCVA only as per SOC History Clinical exam and IOP OCT Adverse event recording STATISTICS AND DATA ANALYSIS
1. SIZE OF SAMPLE Sample size: Data was used from the BEAVRS database (4) and the PIVOT study (17) to estimate an anticipated primary anatomical success rate of 94% based on our entry case criteria. A noninferiority margin of 10% is considered appropriate because air tamponade is convenient for the patients and provides rapid visual recovery as well as early lifting of driving and air travel restrictions. A sample size of 75 per arm (including allowing for a 7% drop out rate) is required for 80% power (at a 5% significance level) to conclude that air tamponade is non-inferior to gas tamponade in the repair of RRD with retinal breaks above 3 and 9 o'clock.
Ten centres will be invited including Liverpool (Manchester, Sheffield, Birmingham, Coventry, Sunderland, Middlesborough, Edinburgh, Kings College, TBC). Recruitment will occur over 18 months i.e., \~1 recruits per centre per month.
2. HEALTH ECONOMICS ANALYSIS Understanding the importance of costs in NHS care a health economic evaluation has been included with co-applicants at Bangor University. Overarching approach: A cost-effectiveness analysis will be undertaken from an NHS perspective. Primary cost-effectiveness analysis using visual acuity outcomes based on the main trial. Secondary cost-utility analysis using the EQ-5D-3L with vision bolt-on.
REGULATORY ISSUES
1. ETHICS APPROVAL The Chief Investigator will obtain approval from the Research Ethics Committee and Health Research Authority (HRA) approval. The study will be submitted to each proposed research site for Confirmation of Capacity and Capability. The study will be conducted in accordance with the recommendations for physicians involved in research on human subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions.
2. CONFIDENTIALITY The Chief Investigator will preserve the confidentiality of participants taking part in the study and will abide by the Data Protection Act (GDPR 2018). All data will be entered into the hospital EPR system which is password protected and uses hospital servers for backup. Anonymised data export will occur at end of the study using study numbers only.
3. INDEMNITY The Liverpool University Hospitals NHS Foundation Trust will provide NHS Indemnity Cover as the sponsor of this study.
4. SPONSOR The Liverpool University Hospitals NHS Foundation Trust will act as Sponsor for this study and be the coordinating site.
5. FUNDING Funding has been obtained from the St. Paul's Eye Research Foundation.
6. AUDITS The study may be subject to risk-based monitoring, inspection and audit by the Liverpool University Hospitals NHS Foundation Trust under their remit as sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research Governance Framework for Health and Social Care (2nd edition).
7. MONITORING AND AUDITING The CI will ensure there are adequate quality and number of monitoring activities conducted by the study team. This will include adherence to the protocol, procedures for consenting and ensure adequate data quality.
8. TRAINING The CI will review and provide assurances of the training and experience of all staff working on this study. Appropriate training records will be maintained in the study files.
Study surgeons will be NHS consultant vitreoretinal surgeons at least 3 years post-certificate of completion of training, and their surgical fellows who must have had at least 4 months experience of VR surgery to participate. They will have been routinely performing vitrectomy for RRD. The intervention of using air instead of gas requires no additional expertise.
STUDY MANAGEMENT The Trial Management Group will comprise all co-applicants and will meet monthly. Day-to-day running of the trial will be undertaken by a Clinical Fellow, and CI, who will meet at least weekly.
A Trial Steering Committee (TSC) will be convened in accordance with National Institute for Health and Care Research (NIHR) Guidelines, and a TSC Terms of Reference, to review the protocol prior to trial commencement and then meet at least twice yearly. Similarly, a Data Monitoring and Ethics Committee (DMEC) will be convened per NIHR guidance and tasked to review safety data at intervals they determine as appropriate, consistent with NIHR guidance and a trial specific DMEC Charter.
A physical trial master file (TMF) will be maintained at the lead site, Liverpool and contain all correspondence with and reports/letters from investigators, research ethics committees (REC), and other regulatory authorities, an up-to-date version of the study protocol, and original source data worksheets. An investigator site file will be maintained in all contributing units.
All approvals including national permissions will be in place at participating centres prior to participant enrolment. All trial investigators are required to undertake Good Clinical Practice (GCP) training, maintain site files, and these will be in order before the Sponsor agrees to open the study.
The study will be submitted to and receive a favourable opinion for a UK Research Ethics Committee (REC) and will require authorisation for each participating site prior to enrolling participants. The CI will prepare a final report in accordance with NIHR requirements.
The study will be registered on ClinicalTrials.gov prior to commencement and the protocol will be made publicly available before data lock.
END OF STUDY The study will be deemed complete when all data collection is completed and the analyses have been fully performed, and data has been locked which is anticipated to be after three years from the start of the study. End of study declaration and final study report will be submitted to HRA/REC and sponsor notifying them of the conclusion of the study. All data will be held electronically.
All documents will be achieved. Data will be archived for 10 years after the end of the study in line with the sponsor's standard operating procedure on archiving.
ARCHIVING Data and all appropriate documentation will be stored for a minimum of 10 years after the completion
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 150
- Primary uncomplicated RRD undergoing vitrectomy.
- Phakic and pseudophakic eyes
- Retinal breaks superiorly between 3 and 9 o'clock, and that are separated by less than 4 clock hours.
- Absence of PVD
- Age 40 years or younger
- PVR grade C or above
- Aphakia or anterior chamber lens
- Retinal breaks greater than 1 clock hour in size
- Retinal breaks that exist below 3 and 9 o'clock on both the nasal and temporal sides.
- Retinal breaks at or posterior to the vessel arcades
- Current or previous -6D myopia or greater (or axial length >26millimetres (mm))
- Chronic RRD judged by the presence of subretinal bands and other signs of -chronicity or by history of visual loss for >28 days.
- Significant inflammation, choroidal detachments, hypotony (<6 millimetres of mercury (mmHg) preop)
- Previous open-globe injury, or endophthalmitis
- Current or previous posterior uveitis or choroiditis
- Any intraocular surgical procedure within 4 weeks other than laser/cryotherapy
- Any other condition that, in the opinion of the investigator, would prevent the participant from granting informed consent or complying with the protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Primary anatomical success 6 months Primary anatomical success at 24 weeks assessed by clinical examination by a retinal surgeon. The Outcome is binary with either 'successful retinal reattachement' or 'failed surgery'
- Secondary Outcome Measures
Name Time Method Post op visual acuity 10 days, 6 weeks and 24 weeks Postoperative visual acuity at 10 days, 6 and 24 weeks measured either in Snellen or logMAR
Intraocular pressure Day 1, 10 and 6 and 24 weeks Day 1, Day 10-, 6- and 24-weeks intraocular pressure measured in mmHg
Quality of Life measures 10 days, 6 and 24 weeks Generic and vision related quality of life using the Euro quality of Life and Visual function questionnaire at 10 days, 6 and 24 weeks postoperatively. These questionnaires have sections relating to ocular health eg vision, ocular pain etc and impact on daily activities. They create a composite score combining each section, which ranges from 0-100 with higher scores reflecting better vision related quality of life.
Patient Satisfaction 10 days, 6 and 24 weeks Patient satisfaction with treatment using the Macular Disease Treatment Satisfaction Questionnaire at 10 days, 6 and 24 weeks. This questionnaire is a self administered questionnaire with a 7 point (0-6) scoring over 14 domains with a total score of 0-72, with higher scores reflecting greater satisfaction