Zhongshan angle-closure prevention (ZAP) study
| ISRCTN | ISRCTN45213099 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN45213099 |
| Secondary identifying numbers | 1 |
- Submission date
- 16/01/2008
- Registration date
- 06/05/2008
- Last edited
- 30/05/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Eye Diseases
Plain English Summary
Current plain English summary as of 17/01/2022:
Background and study aims
Glaucoma is the leading cause of irreversible blindness. Primary angle closure glaucoma (PACG) is the more severe of the two major types of glaucoma. If you have healthy eyes, the fluid in your eye drains away through drainage channels. In some people the eye is shaped differently and the drainage area is very narrow (narrow drainage angles). Under certain circumstances the drain can completely close off, so your eye pressure increases, injuring your optic nerve and damaging your vision. This is considered an attack of angle closure glaucoma. Laser peripheral iridotomy (LPI) is the first-line treatment for PACG. LPI uses a laser beam to create a small hole in your iris, unblocking the drainage channels. LPI is also very effective at preventing symptoms developing in the unaffected eye of patients who have suffered the condition in the other eye. However, so far no conclusions can be drawn regarding the use of prophylactic (preventative) LPI in persons with narrow drainage angles and without any symptoms or signs of active glaucoma. To determine the case for performing prophylactic LPI for all people with narrow angles (1 in 5 Chinese women over the age of 60 fall into this category), it is important to identify how many people with narrow angles will eventually suffer acute symptoms or develop glaucoma. Equally, it is important to know if LPI will reduce this risk, and whether there is any significant adverse risk associated with early LPI treatment. This study aims to assess whether LPI is safe and effective at preventing the development of primary angle closure in high-risk angle-closure patients. The study also specifically aims to answer the question of whether there are any particular features that help to predict who will go on to develop angle closure.
Who can participate?
Guangzhou city residents aged 50 to 70 with narrow drainage angles.
What does the study involve?
The right and left eyes of each participant are randomly allocated to LPI treatment or current standard treatment only. Both treated and untreated eyes are examined on follow-up visits after 2 weeks, 6 months, 18 months, 36 months, 54 months and 72 months.
What are the possible benefits and risks of participating?
Participants will obtain regular and careful medical support from a qualified team of medical experts. There are no obvious risks in participating in this study.
Where is the study run from?
University College London (UK).
When is the study starting and how long is it expected to run for?
March 2008 to February 2017. Patient re-examination commencing 2022 (12+ year follow-up)
Who is funding the study?
1. Fight for Sight (UK)
2. Sun Yat-sen University (China)
3. Wilmer Eye Institute (USA).
4. Ministry of Education of the People's Republic of China (China)
5. National Natural Science Foundation of China (China)
6. The State Key Laboratory, Zhongshan Ophthalmic Center & SunYat-Sen University (China)
Who is the main contact?
1. Prof. Paul J Foster (p.foster@ucl.ac.uk)
2. Prof. Mingguang He (mingguang_he@yahoo.com)
3. Prof. David S Friedman (david_friedman@meei.harvard.edu)
Previous plain English summary:
Background and study aims
Glaucoma is the leading cause of irreversible blindness. Primary angle closure glaucoma (PACG) is the more severe of the two major types of glaucoma. If you have healthy eyes, the fluid in your eye drains away through drainage channels. In some people the eye is shaped differently and the drainage area is very narrow (narrow drainage angles). Under certain circumstances the drain can completely close off, so your eye pressure increases, injuring your optic nerve and damaging your vision. This is considered an attack of angle closure glaucoma. Laser peripheral iridotomy (LPI) is the first-line treatment for PACG. LPI uses a laser beam to create a small hole in your iris, unblocking the drainage channels. LPI is also very effective at preventing symptoms developing in the unaffected eye of patients who have suffered the condition in the other eye. However, so far no conclusions can be drawn regarding the use of prophylactic (preventative) LPI in persons with narrow drainage angles and without any symptoms or signs of active glaucoma. To determine the case for performing prophylactic LPI for all people with narrow angles (1 in 5 Chinese women over the age of 60 fall into this category), it is important to identify how many people with narrow angles will eventually suffer acute symptoms or develop glaucoma. Equally, it is important to know if LPI will reduce this risk, and whether there is any significant adverse risk associated with early LPI treatment. This study aims to assess whether LPI is safe and effective at preventing the development of primary angle closure in high-risk angle-closure patients. The study also specifically aims to answer the question of whether there are any particular features that help to predict who will go on to develop angle closure.
Who can participate?
Guangzhou city residents aged 50 to 70 with narrow drainage angles.
What does the study involve?
The right and left eyes of each participant are randomly allocated to LPI treatment or current standard treatment only. Both treated and untreated eyes are examined on follow-up visits after 2 weeks, 6 months, 18 months, 36 months, 54 months and 72 months.
What are the possible benefits and risks of participating?
Participants will obtain regular and careful medical support from a qualified team of medical experts. There are no obvious risks in participating in this study.
Where is the study run from?
University College London (UK).
When is the study starting and how long is it expected to run for?
March 2008 to February 2017
Who is funding the study?
1. Fight for Sight (UK)
2. Sun Yat-sen University (China)
3. Wilmer Eye Institute (USA).
4. Ministry of Education of the People's Republic of China (China)
5. National Natural Science Foundation of China (China)
Who is the main contact?
1. Prof. Paul J Foster (p.foster@ucl.ac.uk)
2. Prof. Mingguang He (mingguang_he@yahoo.com)
3. Prof. David S Friedman (david.friedman@jhu.edu)
Contact information
Scientific
University College London
Institute of Ophthalmology
11-43 Bath Street
London
EC1V 9EL
United Kingdom
| Phone | +44 (0)20 7608 6899 |
|---|---|
| p.foster@ucl.ac.uk |
Study information
| Study design | Single-centre randomised controlled trial (not masked) |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Available in Chinese with English translation upon request |
| Scientific title | A randomised controlled trial of prevention of angle-closure glaucoma in China |
| Study acronym | ZAP |
| Study hypothesis | That laser iridotomy helps to prevent primary angle-closure (a major risk factor for glaucoma) in Chinese adults aged 50 years and older. |
| Ethics approval(s) | Current ethics approval as of 17/01/2022: 1. Ethical Review Board of Zhongshan Ophthalmic Centre (China), November 2002 2. London School of Hygiene and Tropical Medicine (UK), 17/03/2008, ref: 5267 Extension study: 1. Zhongshan Ophthalmic Centre (China), 28/01/2016, ref: Zhongshan Ophthalmic Center Medical Ethical Committee [2007] No.12 2. London School of Hygiene and Tropical Medicine (UK), 05/03/2011, ref: A240 5267 Extended Follow-up Study: Approved 01/11/2021, Zhongshan Ophthalmic Center Medical Ethical Committee (Zhongshan Ophthalmic Centre, China) Previous ethics approval: 1. Ethical Review Board of Zhongshan Ophthalmic Centre (China), November 2002 2. London School of Hygiene and Tropical Medicine (UK), 17/03/2008, ref: 5267 Extension study: 1. Zhongshan Ophthalmic Centre (China), 28/01/2016, ref: Zhongshan Ophthalmic Center Medical Ethical Committee [2007] No.12 2. London School of Hygiene and Tropical Medicine (UK), 05/03/2011, ref: A240 5267 |
| Condition | Angle-closure glaucoma |
| Intervention | Current intervention as of 17/01/2022: The right and left eyes of each participant will be randomly allocated to the intervention treatment or no treatment (control). Intervention treatment: Laser peripheral iridotomy (LPI) by sequential argon then Nd:YAG laser. Duration of the laser treatment is about 5 minutes. Control: No intervention (current standard treatment only) Each participant will be examined at baseline, 2 weeks, 6, 18, 30 and 42 months. Each participant will be further examined at 54 and 72 months after LPI. Re-examination to assess visual function, supplementary surgery (i.e. cataract surgery), and to document any differences in risk factor profile for glaucomatous loss of vision (intraocular pressure, peripheral anterior synechiae) between treated and untreated eyes at 12+ from intervention. Previous intervention: The right and left eyes of each participant will be randomly allocated to the intervention treatment or no treatment (control). Intervention treatment: Laser peripheral iridotomy (LPI) by sequential argon then Nd:YAG laser. Duration of the laser treatment is about 5 minutes. Control: No intervention (current standard treatment only) Each participant will be examined at baseline, 2 weeks, 6, 18, 30 and 42 months. Added 20/09/2016: Each participant will be further examined at 54 and 72 months after LPI. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | The following will be assessed on each of the scheduled follow-up (6, 18, 30 and 42 months): 1. Raised intraocular pressure (either with or without symptoms). Intraocular pressure greater than 24 mmHg verified on two consecutive measurements on separate days. These patients will be further identified as having open, partially-closed or completely closed angles on dark room gonioscopy and anterior segment optical coherence tomography (AS-OCT). 2. Peripheral anterior synechiae 3. Glaucomatous optic neuropathy If participants are felt to have met a failure criterion, they are re-assessed (by examination with one of the senior investigators) within the next 2 weeks to confirm. The failure will then be classified as having occurred at 6, 18, 30 or 42 months (end of the study). Added 20/09/2016: Outcomes will also be assessed at 54 and 72 months. If participants are felt to have met a failure criterion, they are re-assessed (by examination with one of the senior investigators) within the next 2 weeks to confirm. The failure will then be classified as having occurred at 54 or 72 months (end of the study). |
| Secondary outcome measures | The following will be assessed on each of the scheduled follow-up (6, 18, 30 and 42 months): 1. Specular microscopy measures of corneal endothelial cell loss 2. Formation of lens opacity 3. Anterior segment optical coherence tomography measures (qualitative and quantitative) of ocular anterior segment anatomy 4. Digital iris photograph measures of iris 5. Ultrasound biomicroscopy measurements of ocular anterior segment anatomy If participants are felt to have met a failure criterion, we will re-assess (by examination with one of the senior investigators) within the next 2 weeks to confirm. The failure will then be classified as having occurred at 6, 18, 30 or 42 months (end of the study). Added 20/09/2016: Outcomes will also be assessed at 54 and 72 months. If participants are felt to have met a failure criterion, they are re-assessed (by examination with one of the senior investigators) within the next 2 weeks to confirm. The failure will then be classified as having occurred at 54 or 72 months (end of the study). |
| Overall study start date | 01/03/2008 |
| Overall study end date | 28/02/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 50 Years |
| Sex | Both |
| Target number of participants | 1,100 |
| Participant inclusion criteria | 1. Anatomically narrow drainage angles in the anterior segment of the eye 2. No evidence of primary angle-closure (high pressure or peripheral anterior synechiae) 3. Aged greater than or equal to 50 years |
| Participant exclusion criteria | 1. Inability or unwillingness to give informed consent 2. Raised intraocular pressure, peripheral anterior synechiae or glaucomatous optic neuropathy 3. Previous intraocular surgery |
| Recruitment start date | 01/09/2008 |
| Recruitment end date | 22/10/2010 |
Locations
Countries of recruitment
- Australia
- China
- England
- United Kingdom
- United States of America
Study participating centres
London
EC1V 9EL
United Kingdom
Peter Howson Wing
Level 7, 32 Gisborne Street
East Melbourne
Melbourne
3002
Australia
Boston
02114
United States of America
State Key Laboratory of Ophthalmology
Clinical Research Center
Sun Yat-Sen University
Guangzhou
510080
China
Sponsor information
University/education
Gower Street
London
WC1E 6BT
England
United Kingdom
| Phone | +44 (0)20 7608 6854 |
|---|---|
| h.jones@ucl.ac.uk | |
| Website | http://www.ucl.ac.uk/ |
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Government
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Fight for Sight
- Location
- United Kingdom
Private sector organisation / Universities (academic only)
- Alternative name(s)
- SYSU
- Location
- China
Government organisation / National government
- Alternative name(s)
- 中华人民共和国教育部, Министерство образования Китайской Народной Республики, 中華人民共和国教育部, Bildungsministerium der Volksrepublik China, Ministry of Education of China, Ministry of Education, The People's Republic of China, Ministry of Education of the Central People's Government, State Education Commission, MOE
- Location
- China
Government organisation / National government
- Alternative name(s)
- Chinese National Science Foundation, Natural Science Foundation of China, National Science Foundation of China, NNSF of China, NSF of China, 国家自然科学基金委员会, National Nature Science Foundation of China, Guójiā Zìrán Kēxué Jījīn Wěiyuánhuì, NSFC, NNSF, NNSFC
- Location
- China
No information available
No information available
Results and Publications
| Intention to publish date | 31/03/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Current publication and dissemination plan as of 17/01/2022: The main findings of the ZAP study were published in The Lancet in 2019 and presented at academic conferences. A range of publications dealing with clinical features of treated and untreated patients have been published by the same authors (He, Foster, Friedman). An extended follow-up is underway in 2022, with a view to publish in 2023 Previous publication and dissemination plan: The main findings of the ZAP study will be published in peer-reviewed journals before the end of 2017 and presented at academic conferences. |
| IPD sharing plan | Current individual participant data (IPD) sharing statement as of 17/01/2022: The datasets generated and/or analysed during the current study are available from Prof. Paul Foster (p.foster@ucl.ac.uk), Prof Friedman (david_friedman@meei.harvard.edu), and Prof. Mingguang He (mingguang.he@unimelb.edu.au; mingguang_he@yahoo.com) on reasonable request. Previous individual participant data (IPD) sharing statement: The datasets generated and/or analysed during the current study are available from Prof. Paul Foster (p.foster@ucl.ac.uk) and Prof. Mingguang He (mingguang.he@unimelb.edu.au; mingguang_he@yahoo.com) on reasonable request. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | Visual symptoms | 01/07/2012 | Yes | No | |
| Results article | results | 20/04/2019 | Yes | No | |
| Results article | Cataract progression | 02/05/2022 | 03/05/2022 | Yes | No |
| Results article | Iris volume change | 26/05/2023 | 30/05/2023 | Yes | No |
Editorial Notes
30/05/2023: Publication reference added.
03/05/2022: Publication reference added.
17/01/2022: The following changes have been made:
1. The public title has been changed from "Zhongshan angle-closure prevention study" to "Zhongshan angle-closure prevention (ZAP) study".
2. The acronym has been changed from ZAAP to ZAP.
3. The ethics approval has been updated.
4. The intervention has been updated.
5. The trial participating centre "UCL Institute of Ophthalmology & Moorfields Eye Hospital", "Centre for Eye Research Australia (CERA)", "Massachusetts Eye and Ear Infirmary", and "Zhongshan Ophthalmic Center" have been added and the trial participating centre "University College London" has been removed.
6. The plain English summary has been updated.
7. The individual participant data (IPD) sharing statement has been updated.
8. The publication and dissemination plan has been updated.
9. The intention to publish date has been changed from 31/12/2017 to 13/03/2019.
10. The funder "The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center" has been added.
18/03/2019: Publication reference added.
20/09/2016: The overall trial end date was changed from 28/02/2011 to 28/02/2017.
