Ignite Creation Date:
2024-05-05 @ 5:07 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00386958
Status:
COMPLETED
Last Update Posted:
2016-08-23
First Post:
2006-10-11
Brief Title:
A Clinical Trial of Povidone-Iodine for the Treatment of Bacterial Corneal Ulcers
Sponsor:
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Organization:
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Study Overview
Official Title:
A Clinical Trial of Povidone-Iodine for the Treatment of Bacterial Corneal Ulcers
Status:
COMPLETED
Status Verified Date:
2006-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Bacterial corneal ulcers are a leading cause of pediatric blindness in underdeveloped countries due to a lack of antibiotic availability and affordability among other reasons Povidone-iodine an inexpensive and readily available broad-spectrum antimicrobial agent may be an effective and affordable treatment for corneal ulcers allowing preservation of sight for those afflicted with this disease
Detailed Description:
Hypothesis to be tested
Infectious corneal ulceration causes corneal scarring opacification and blindness in hundreds of thousands of children annually In developing countries it is the number one cause of avoidable blindness in children While in some cases the cornea was healthy prior to ulceration in others xerophthalmia trachoma rubeola trauma or some other cause previously compromised the cornea Even when the ulceration is associated with one of the above etiologies it is usually the bacterial corneal ulcer that directly leads to blindness in the short-term In many countries few of these infections are properly treated with appropriate antimicrobial agents due to a number of factors including cost availability and effectiveness If a topical antimicrobial agent were readily available in developing countries which is also inexpensive and effective many of these ulcers could be cured before scarring and blindness result
The best candidate for such a medication is povidone-iodine ophthalmic solution It has already been proven the best agent to sterilize the ocular surface before and after eye surgery and to prevent conjunctivitis in newborn babies It was also shown an effective treatment against bacterial conjunctivitis in children Povidone-iodine ophthalmic solution can be prepared in a local hospital or clinic by mixing the powder with an ophthalmic saline solution bringing the cost of a 10-ml bottle to less than US 010 By contrast in the Philippines a 10 ml bottle of Neosporin ophthalmic solution cost about 400 and it may take a few bottles to cure a bacterial corneal ulcer For far less than a US dollar a corneal ulcer could be fully cured Povidone-iodine has the widest antimicrobial spectrum of any known topical medication It has been shown to be effective against all bacteria fungi and viruses No true resistance to povidone-iodine has ever been demonstrated Allergic reactions are rare Thus if any medication could serve the purpose for this study it would be povidone-iodine
The primary research question is whether povidone-iodine ophthalmic solution is effective in healing bacterial corneal ulcers which if proven would have a dramatic effect in reducing pediatric blindness
The number of subjects was determined from the primary outcome measure of non-inferiority to achieve a minimum of a one-day difference between the control and investigative groups with povidone-iodine being compared to the control medication at each study site The control medications are Neosporin ophthalmic solution in Manila and ciprofloxacin ophthalmic solution in the two combined Indian sites Hyderabad and Tiruchirapalli for a total of four study arms The number of recruits was calculated to achieve 90 power for detecting non-inferiority using t-tests with a level of significance of 005 for comparing mean time to cure Cure is defined as closure of the epithelial defect with no inflammatory signs other than minimal injection
Subjects provided written consent As appropriate child assent was also obtained At each study site subjects were allocated to receive either povidone-iodine or the control medication If corneal ulcers were present bilaterally one eye was randomized to receive povidone-iodine while the other received the control medication standard for that center All subjects were hospitalized for at least 7 days for careful monitoring and appropriate treatment To assure compliance all subjects had their medications administered by medical personnel
Treatment
The study medication is 125 povidone-iodine and the control medications are Neosporin ophthalmic solution in Manila Philippines and ciprofloxacin 03 ophthalmic solution in Hyderabad and Tiruchirapalli India These medications are the standard of care at each respective study site The only eye medication permitted beside povidone-iodine 125 ophthalmic solution and the control medications Neosporin and ciprofloxacin is atropine ophthalmic solution to reduce intraocular inflammation and prevent synechiae The atropine solution is administered to the affected eyes twice a day Subjects less than one year old receive a 025 solution those aged one to three years receive 05 and those older than 3 years receive the 1 solution
The dosing schedule of povidone-iodine 125 or control ophthalmic solutions is as follows
1 For the first three days one drop of the medication is applied every hour
2 Day 4 and thereafter hourly while awake When asleep sleep not to exceed 9 hours drops are administered every three hours All cases are treated with this intense drop therapy for a minimum of 5 days unless criteria for change in therapy are met see below
3 At 5 days If there is no deterioration in any factor see below and improvement in at least one factor other than epithelial defect size on 2 consecutive examinations dosing frequency is decreased to every 2 hours while awake about 8 timesday for 2 days then 4 timesday until discharge If status remained unchanged at Day 5 intense drop therapy continues for 5 more days
4 If at 10 days the status is unchanged the subject exits the study
All patients are examined daily and have their visual acuity and ocular examination documented The daily eye examination findings are scored and recorded for the following six factors
1 Visual acuity
2 Inflammatory signs
3 Stromal infiltrate dimensions
4 Epithelial defect dimensions
5 MELT
6 Tissue firmness including keratic precipitate KPanterior chamberACcellular reaction AC fibrin and hypopyon status
The daily assessment of the ulcer status is classified as cured improved persistent worsening or failure
Criteria for Change in Therapy
Within the first 48 hours treatment is changed for deterioration in all factors or appearance of a descemetocele After 48 hours of treatment treatment is changed for deterioration in one or more of the following factors on 2 consecutive examinations stromal infiltrate melt or two or more signs or symptoms of inflammation Epithelial defect size is used only for assessing status not for change in medication The new treatment is left to the discretion of the ophthalmologist
Culture Technique
All subjects undergo microbiological analysis of the corneal ulcer upon intake into the study A spatula is applied to the cornea of the affected eyes and blood agar and chocolate agar plates and brain heart infusion broth BHI are streaked for each patient Cultures are repeated daily until two negative cultures are obtained If the cultures are positive for any organism that organism is considered the infecting agent Each culture plate is incubated for at least seven days and the colony forming units are differentiated and enumerated by standard bacteriological techniques including the VPI technique for anaerobic bacteria No culture growth at seven days constitutes a negative culture
Infectious corneal ulceration causes corneal scarring opacification and blindness in hundreds of thousands of children annually In developing countries it is the number one cause of avoidable blindness in children While in some cases the cornea was healthy prior to ulceration in others xerophthalmia trachoma rubeola trauma or some other cause previously compromised the cornea Even when the ulceration is associated with one of the above etiologies it is usually the bacterial corneal ulcer that directly leads to blindness in the short-term In many countries few of these infections are properly treated with appropriate antimicrobial agents due to a number of factors including cost availability and effectiveness If a topical antimicrobial agent were readily available in developing countries which is also inexpensive and effective many of these ulcers could be cured before scarring and blindness result
The best candidate for such a medication is povidone-iodine ophthalmic solution It has already been proven the best agent to sterilize the ocular surface before and after eye surgery and to prevent conjunctivitis in newborn babies It was also shown an effective treatment against bacterial conjunctivitis in children Povidone-iodine ophthalmic solution can be prepared in a local hospital or clinic by mixing the powder with an ophthalmic saline solution bringing the cost of a 10-ml bottle to less than US 010 By contrast in the Philippines a 10 ml bottle of Neosporin ophthalmic solution cost about 400 and it may take a few bottles to cure a bacterial corneal ulcer For far less than a US dollar a corneal ulcer could be fully cured Povidone-iodine has the widest antimicrobial spectrum of any known topical medication It has been shown to be effective against all bacteria fungi and viruses No true resistance to povidone-iodine has ever been demonstrated Allergic reactions are rare Thus if any medication could serve the purpose for this study it would be povidone-iodine
The primary research question is whether povidone-iodine ophthalmic solution is effective in healing bacterial corneal ulcers which if proven would have a dramatic effect in reducing pediatric blindness
The number of subjects was determined from the primary outcome measure of non-inferiority to achieve a minimum of a one-day difference between the control and investigative groups with povidone-iodine being compared to the control medication at each study site The control medications are Neosporin ophthalmic solution in Manila and ciprofloxacin ophthalmic solution in the two combined Indian sites Hyderabad and Tiruchirapalli for a total of four study arms The number of recruits was calculated to achieve 90 power for detecting non-inferiority using t-tests with a level of significance of 005 for comparing mean time to cure Cure is defined as closure of the epithelial defect with no inflammatory signs other than minimal injection
Subjects provided written consent As appropriate child assent was also obtained At each study site subjects were allocated to receive either povidone-iodine or the control medication If corneal ulcers were present bilaterally one eye was randomized to receive povidone-iodine while the other received the control medication standard for that center All subjects were hospitalized for at least 7 days for careful monitoring and appropriate treatment To assure compliance all subjects had their medications administered by medical personnel
Treatment
The study medication is 125 povidone-iodine and the control medications are Neosporin ophthalmic solution in Manila Philippines and ciprofloxacin 03 ophthalmic solution in Hyderabad and Tiruchirapalli India These medications are the standard of care at each respective study site The only eye medication permitted beside povidone-iodine 125 ophthalmic solution and the control medications Neosporin and ciprofloxacin is atropine ophthalmic solution to reduce intraocular inflammation and prevent synechiae The atropine solution is administered to the affected eyes twice a day Subjects less than one year old receive a 025 solution those aged one to three years receive 05 and those older than 3 years receive the 1 solution
The dosing schedule of povidone-iodine 125 or control ophthalmic solutions is as follows
1 For the first three days one drop of the medication is applied every hour
2 Day 4 and thereafter hourly while awake When asleep sleep not to exceed 9 hours drops are administered every three hours All cases are treated with this intense drop therapy for a minimum of 5 days unless criteria for change in therapy are met see below
3 At 5 days If there is no deterioration in any factor see below and improvement in at least one factor other than epithelial defect size on 2 consecutive examinations dosing frequency is decreased to every 2 hours while awake about 8 timesday for 2 days then 4 timesday until discharge If status remained unchanged at Day 5 intense drop therapy continues for 5 more days
4 If at 10 days the status is unchanged the subject exits the study
All patients are examined daily and have their visual acuity and ocular examination documented The daily eye examination findings are scored and recorded for the following six factors
1 Visual acuity
2 Inflammatory signs
3 Stromal infiltrate dimensions
4 Epithelial defect dimensions
5 MELT
6 Tissue firmness including keratic precipitate KPanterior chamberACcellular reaction AC fibrin and hypopyon status
The daily assessment of the ulcer status is classified as cured improved persistent worsening or failure
Criteria for Change in Therapy
Within the first 48 hours treatment is changed for deterioration in all factors or appearance of a descemetocele After 48 hours of treatment treatment is changed for deterioration in one or more of the following factors on 2 consecutive examinations stromal infiltrate melt or two or more signs or symptoms of inflammation Epithelial defect size is used only for assessing status not for change in medication The new treatment is left to the discretion of the ophthalmologist
Culture Technique
All subjects undergo microbiological analysis of the corneal ulcer upon intake into the study A spatula is applied to the cornea of the affected eyes and blood agar and chocolate agar plates and brain heart infusion broth BHI are streaked for each patient Cultures are repeated daily until two negative cultures are obtained If the cultures are positive for any organism that organism is considered the infecting agent Each culture plate is incubated for at least seven days and the colony forming units are differentiated and enumerated by standard bacteriological techniques including the VPI technique for anaerobic bacteria No culture growth at seven days constitutes a negative culture
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 10274-02 | None | None | None |