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CTRI Number  CTRI/2024/04/065756 [Registered on: 16/04/2024] Trial Registered Prospectively
Last Modified On: 15/04/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Single Arm Study 
Public Title of Study   A pilot study to assess the efficiency of Lamivudine, a drug used to treat HIV, in retinal edema due to vein occlusion 
Scientific Title of Study   Pilot study to assess the efficacy of oral Lamivudine for macular edema due to retinal vein occlusions 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Siddharth Narendran  
Designation  Medical Consultant 
Affiliation  Aravind Eye Hospital, Coimbatore 
Address  Clinical research Department, Aravind Eye Hospital Avinashi Road Sitra Coimbatore

Coimbatore
TAMIL NADU
641014
India 
Phone  9442566222  
Fax    
Email  siddharth@aravind.org  
 
Details of Contact Person
Scientific Query  
Name  Dr Siddharth Narendran  
Designation  Medical Consultant 
Affiliation  Aravind Eye Hospital, Coimbatore 
Address  Clinical Research Department, Aravind Eye Hospital Avinashi Road Sitra Coimbatore

Coimbatore
TAMIL NADU
641014
India 
Phone  9442566222  
Fax    
Email  siddharth@aravind.org  
 
Details of Contact Person
Public Query  
Name  Dr Siddharth Narendran  
Designation  Medical Consultant 
Affiliation  Aravind Eye Hospital, Coimbatore 
Address  Clinical Research Department, Aravind Eye Hospital Avinashi Road Sitra Coimbatore

Coimbatore
TAMIL NADU
641014
India 
Phone  9442566222  
Fax    
Email  siddharth@aravind.org  
 
Source of Monetary or Material Support  
Aravind Eye Hospital, 1, Anna Nagar, Madurai, Tamil Nadu, India, PIN code: 625020 
 
Primary Sponsor  
Name  Aravind Eye Hospital  
Address  1, Anna Nagar, Madurai, Tamil Nadu, India, PIN code: 625020 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Siddharth Narendran  Aravind Eye Hospital, Coimbatore  Department of Retina
Coimbatore
TAMIL NADU 		 9442566222

siddharth@aravind.org 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Human Ethics Committee - PSG Institute of Medical Sciences and Research  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: H348||Other retinal vascular occlusions,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Lamivudine  oral tablet - 150mg twice daily for 3 months 
Comparator Agent  nil  nil 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  75.00 Year(s)
Gender  Both 
Details  1)patients with documented presence of intraretinal or subretinal fluid secondary to Retinal Vein Occlusion.
2)patients with ability and willingness to comply with treatment and follow up process and to understand and sign the informed consent form. 
 
ExclusionCriteria 
Details  Study Eye only:
1)Evidence of iris, anterior chamber angle or retinal/optic disc neovascularization
2)Ocular disorders/additional eye disease, which in the opinion of the Investigator may confound interpretation of study results, compromise protocol assessments or are likely to require intervention during the study, including, but not limited to, atrophy of the retinal pigment epithelium, sub-retinal fibrosis, organized hard exudate plaque, clinically significant diabetic macular edema, retinal detachment, macular hole, vitreomacular traction, macular epiretinal membrane, clinically significant cataract, vitreal opacities or hemorrhage, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa or choroidal neovascularization of any cause (e.g., Age-related Macular Degeneration (AMD), ocular histoplasmosis, toxoplasmosis, or pathologic myopia)
3)Receipt within the past 6 months prior to the Screening Visit of any intraocular or periocular surgery (including refractive surgery, cataract surgery), or intravitreal (IVT) injection, or planned intraocular surgery or procedure during the study
Both Eyes:
1)History of glaucoma or an IOP greater than 21 mmHg
2)Previous use of intraocular or periocular steroids within 3 months prior to baseline, or dexamethasone intravitreal implant within 6 months prior to baseline
3)History of, or presence of uveitis, presence of intraocular inflammation
4)History of intravitreal use of anti-VEGF drugs (e.g. ranibizumab，bevacizumab，aflibercept,etc), macular laser photocoagulation (focal/grid)，panretinal laser photocoagulation, vitrectomy, trabeculectomy or keratoplasty in the study eye at any time prior to baseline. YAG laser treatment or any other intraocular surgeries (e.g. cataract surgery) in the study eye within 6 months prior to the baseline
5)Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens, or optic nerve (e.g., desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol).
6)History of impaired renal or liver function
7)Liver dysfunction (ALT or AST is 2 times higher than the upper limit of normal value in the local laboratory). Renal function impairment (Cr is 1.5 times higher than the upper limit of normal values in the local laboratory)
8)Women in pregnancy and lactation
9)Individuals with HIV, HBV, or who have current/previous use of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) or non-NRTIs
 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
Mean change from baseline in Best-corrected visual acuity (BCVA) [ Time Frame: Baseline to Week 12]. Assessed with Early treatment diabetic retinopathy study (ETDRS) visual acuity testing charts at baseline and Weeks 2,4,8 and 12.  baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks 
 
Secondary Outcome  
Outcome  TimePoints 
Mean change from baseline Center Subfield Macular Thickness (CMT). [ Time Frame: Baseline to Week 12]. Assessed with Spectral Domain Optical Coherence Tomography (SD-OCT) at baseline and Weeks 2,4,8 and 12.  baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks 
Change from baseline in Foveal Avascular Zone (FAZ) and Vessel Density (VD). [ Time Frame: Baseline to Week 12]. Assessed with Optical Coherence Tomography Angiography (OCTA) at baseline and Weeks 2,4,8 and 12  baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks 
Macular Function Using multi-focal electroretinogram (mf-ERG) [ Time Frame: baseline to 12 weeks ] To determine if there is a change in central amplitude responses using mfERG at 12 weeks compared to baseline values  baseline, 12 weeks 
Mean change from baseline in contrast sensitivity. [ Time Frame: Baseline to Week 12]. Assessed with MARS Contrast sensitivity test at baseline and Weeks 2,4,8 and 12.  baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks 
Safety - laboratory parameters [ Time Frame: 12 weeks] assessed by Liver and Renal function tests at baseline and week 12.  baseline, 12 weeks 
 
Target Sample Size   Total Sample Size="30"
Sample Size from India="30" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   01/05/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="0"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   Introduction: 
The most visually threatening complications of retinal vein occlusions include macular edema and neovascularisation. The predominant management of macular edema consists of intravitreal anti-VEGF injections which cause a reduction in macular thickness, which is well demonstrated on Spectral Domain - Optical Coherence Tomography (SD-OCT). In this study, we attempt to study the efficacy and safety of orally administered lamivudine in causing a reduction in macular edema secondary to retinal vein occlusion.
Review of Literature:
Lamivudine is a Nucleoside Reverse Transcriptase Inhibitor (NRTI) being used to control disease activity in People Living with HIV/AIDS (PLHA). Studies have demonstrated anti-inflammatory as well as anti-angiogenic activity of drugs used to treat HIV, including Lamivudine. Lamivudine weakens ERK (extracellular signal regulated kinases) phosphorylation promoted in endothelial cells by VEGF-A. It also depresses VEGF - promoted AKT phosphorylation in endothelial cells. Inhibition of angiogenesis and lymphangiogenesis in endothelial cell line was also studied, leading the authors to conclude that NRTIs negatively regulate angiogenesis and lymphangiogenesis. Since endothelial dysfunction is the cause of macular edema in retinal vein occlusions, we aim to study if orally administered lamivudine can be used for its treatment.
Justification for the study:
The standard of care for macular edema secondary to retinal vein occlusions is intravitreal injection of anti- VEGF agents. This procedure needs sterile operation theatre condition, driving up costs for both the hospital and the patient. Substituting intravitreal injections with oral tablets would reduce costs involved as well as remove attendant risks associated with an invasive procedure such as endophthalmitis. 
Major objective:
To test safety and efficacy of oral lamivudine as treatment for macular edema secondary to retinal vein occlusion and compare outcomes with intravitreal bevacizumab (Avastin) injection for the same indication.
Materials and Methods:
-Pilot interventional single center trial
-Treatment duration: 1 month. After obtaining informed consent, patients clinically diagnosed with retinal vein occlusion and noted to have foveal center - involved macular edema secondary to the RVO, retinal thickness in the central subfield >350 microns as measured by OCT, and visual acuity between 6/12 and 6/60 in the study eye will be recruited. Patients will be administered oral lamivudine 150mg twice daily.
-Primary outcome measures to be measured at the end of 1 month, include best corrected visual acuity and macular edema resolution to be determined by OCT. Safety outcomes include the number of participant withdrawals, number and severity of systemic and ocular toxicities and the number of adverse events. 
Risks and Benefits:
- most common adverse events include nausea, dizziness, fatigue, malaise, headache, dreams, insomnia and skin rash. Laboratory abnormalities are uncommon with lamivudine.
-possible benefits include resolution of macular edema.
Expected Outcome:
Systemic treatment (oral) for the management of retinal vein occlusion induced macular edema.
 
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