Back to resultsComparison of Efficacy Between 100% Platelet-rich Plasma and 100% Serum Eye Drops in Dry Eye Disease
Primary Purpose
Dry Eye Disease
Status
Completed
Phase
Phase 3
Locations
Thailand
Study Type
Interventional
Intervention
100% Autologous platelet rich plasma
100% Autologous serum
Sponsored by
About this trial
This is an interventional treatment trial for Dry Eye Disease
Eligibility Criteria
Inclusion Criteria:
- Aged 18 to less than 75 years.
- Have OSDI scores ≥ 23 or Oxford staining grade ≥ 2.
- Do not have following conditions:
Uncontrolled systemic diseases, active infection, advanced cancer. Pregnant and nursing women. • Have not recently used the following medications/interventions/surgery: Anticoagulants or anti-platelets. Topical undiluted blood products within 3 months. Punctal plug or contact lenses. Ocular surgery within 6 months.
- Do not have active ocular infection/inflammation, abnormal eyelid function or severe meibomian gland dysfunction (MGD stage 4).
- Have no contraindication for blood donations:
Positive human immunodeficiency virus, hepatitis B or C, or syphilis. Anemia (Hb < 11 g/dL) or platelet concentration < 150,000/ml.
- Being able to stop current dry eye treatment for 48 hours before staring trial intervention
- Willing to comply with the 4-week study protocol and provide informed consent.
Exclusion Criteria:
• None
Sites / Locations
- Ophthalmology Department, Ramathibodi Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
100% APRP
100% AS
Arm Description
Patients will be instructed to apply every 2 hours (8 times/day). The currently used bottle will be required to store at 4 C for 24 hours, and the remaining bottles at -20 C in a freezer until day of use.
Patients will be instructed to apply every 2 hours (8 times/day). The currently used bottle will be required to store at 4 C for 24 hours, and the remaining bottles at -20 C in a freezer until day of use.
Outcomes
Primary Outcome Measures
Ocular surface score index (OSDI)
The OSDI is a patient-reported outcome (PRO) questionnaire which was designed by Allergan, Inc. to assess range of ocular symptoms related to chronic dry eye disease and reflect patient's ability of function. It comprised 12 questions which are divided into 3 subscales including ocular symptoms (5 questions), vision-related function (4 questions), and environmental triggers (3 questions). Each of question is rated from 0 to 4 indicating none of the time, some of the time, half of the time, most of the time and all of the time, respectively. The average OSDI is transformed into a score ranged from 0 to 100, with a higher score indicating more severity of dry eye disease. The OSDI is classified as normal (0-12 points), mild (13-22 points), moderate (23-32 points) and severe (33-100).
Ocular surface staining (OSS)
To assess total ocular surface staining, the cornea and conjunctival staining are graded by using Oxford scale guidelines (range grade 0 to 5). The higher score refers to higher severity of dry eye.
Secondary Outcome Measures
Fluorescein break up time (FBUT)
The break up time (seconds) will be measured after fluorescein staining by using a stopwatch starting from the time of complete eye lid opening to the time of the first tear break up appear. The average values of 3 times of FBUT will be used. The reference value for DED diagnosis is used ranged from a cut-off time of less than 10 seconds for dry eye and less than 5 seconds for severe dry eye.
Schirmer's test (ST)
The Schirmer test (ST) was performed using commercially available prepackaged sterile paper strips without anesthesia. The rounded bulb end of the strip was folded and placed in the lateral canthus away from the cornea and left in place for 5 minutes after which the wet strip length was recorded in mm. Tear deficiency is defined if ST is less than 5 mm wetting of the paper after 5 minutes.
Meibum quality and expressibility.
Meibum quality is assessed by applying the pressure on each of 8 glands of the central third of the lower lid on a scale of 0 to 3 for each gland: 0, clear; 1, cloudy; 2, cloudy with debris (granular); and 3, thick, like toothpaste (total score range, 0-24). Higher score indicates the higher severity of meibomian gland dysfunction.
Expressibility is assessed on a scale of 0 to 3 in five glands in the lower or upper lid, according to the number of glands expressible: 0, all glands; 1, three to four glands; 2, one to two glands; and 3, no glands. Higher score indicates the higher severity of meibomian gland dysfunction.
Number of patients with ocular adverse events
All ocular adverse events will be recorded throughout the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04683796
Brief Title
Comparison of Efficacy Between 100% Platelet-rich Plasma and 100% Serum Eye Drops in Dry Eye Disease
Official Title
Comparison of Treatment Efficacy Between 100% Platelet-rich Plasma and 100% Serum Eye Drops in Moderate to Severe Dry Eye Disease: A Randomized Controlled Trial Protocol
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
February 28, 2023 (Actual)
Study Completion Date
March 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mahidol University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Dry eye disease (DED) is a common eye problem, affecting 5% to 50% of the world population. Although the disease is not fatal, it substantially reduces quality of life and creates a high economic burden as high as over 50 billion from a societal perspective. Several biological tear substitutes (e.g., autologous serum (AS), autologous platelet rich plasma (APRP), and autologous platelet lysate (APL)) could effectively improve dry eyes, especially in patients with moderate to severe DED.. However, evidence on their comparative efficacy is controversial. The objective of the study is to compare the efficacy of 100% APRP with 100% AS eye drops in patients with moderate to severe DED.
Detailed Description
The study is a single-center, double-blinded randomized, parallel, non-inferiority trial. Patients will be recruited from out-patient clinic, Department of Ophthalmology, Ramathibodi Hospital, Bangkok and will be randomized to receive either 100% APRP or 100% AS eye drops (1:1 ratio) for 4 weeks. The primary outcomes include ocular surface disease index (OSDI) and ocular surface staining evaluated using the Oxford scale. Secondary outcomes are fluorescein break-up time (FBUT), Schirmer's I test (ST I), meibomian gland parameters and adverse events.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Patients will be randomly allocated to receive either 100% APRP or 100% AS (the same treatment for both eyes).
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Treatment package will be labelled as randomization number. Participants will also be blinded to the treatments they receive by using the identical type of eye drop bottle. Clinical and research staffs involved in the outcome assessments will be blinded to the treatment allocation. Lastly, data analysts will also be blinded.
Allocation
Randomized
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
100% APRP
Arm Type
Experimental
Arm Description
Patients will be instructed to apply every 2 hours (8 times/day). The currently used bottle will be required to store at 4 C for 24 hours, and the remaining bottles at -20 C in a freezer until day of use.
Arm Title
100% AS
Arm Type
Active Comparator
Arm Description
Patients will be instructed to apply every 2 hours (8 times/day). The currently used bottle will be required to store at 4 C for 24 hours, and the remaining bottles at -20 C in a freezer until day of use.
Intervention Type
Drug
Intervention Name(s)
100% Autologous platelet rich plasma
Other Intervention Name(s)
APRP
Intervention Description
Patients' blood (36 ml per tube) will be collected in three 50-ml sterile centrifuge tubes containing 4 ml of 3.2% buffered citrate acid for anticoagulation. Tubes will be centrifuged at 350 g for 10 minutes at 20 C. The two upper layers of the centrifuged blood, the plasma and the superficial buffy coat, will be separated in a sterile manner under a laminar air flow hood. A 1.5 ml aliquot of both final blood products will be transferred into identical opaque eye drop bottles, labelled name, hospital number, dated and sealed.
Intervention Type
Drug
Intervention Name(s)
100% Autologous serum
Other Intervention Name(s)
AS
Intervention Description
Patients' blood (36 ml per tube) will be collected in three 50-ml sterile centrifuge tubes. The tubes will be left standing in an upright position for 1-2 hours to enable blood clot formation at room temperature (18-25 C). The tubes will be centrifuged at 3000 g for 30 minutes at 20 C. The supernatant serum will be aseptically transferred into a sterile syringe to enable filtration through a 0.2 µm pore size membrane filter under a laminar air flow hood. A 1.5 ml aliquot of both final blood products will be transferred into identical opaque eye drop bottles, labelled name, hospital number, dated and sealed.
Primary Outcome Measure Information:
Title
Ocular surface score index (OSDI)
Description
The OSDI is a patient-reported outcome (PRO) questionnaire which was designed by Allergan, Inc. to assess range of ocular symptoms related to chronic dry eye disease and reflect patient's ability of function. It comprised 12 questions which are divided into 3 subscales including ocular symptoms (5 questions), vision-related function (4 questions), and environmental triggers (3 questions). Each of question is rated from 0 to 4 indicating none of the time, some of the time, half of the time, most of the time and all of the time, respectively. The average OSDI is transformed into a score ranged from 0 to 100, with a higher score indicating more severity of dry eye disease. The OSDI is classified as normal (0-12 points), mild (13-22 points), moderate (23-32 points) and severe (33-100).
Time Frame
4 weeks
Title
Ocular surface staining (OSS)
Description
To assess total ocular surface staining, the cornea and conjunctival staining are graded by using Oxford scale guidelines (range grade 0 to 5). The higher score refers to higher severity of dry eye.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Fluorescein break up time (FBUT)
Description
The break up time (seconds) will be measured after fluorescein staining by using a stopwatch starting from the time of complete eye lid opening to the time of the first tear break up appear. The average values of 3 times of FBUT will be used. The reference value for DED diagnosis is used ranged from a cut-off time of less than 10 seconds for dry eye and less than 5 seconds for severe dry eye.
Time Frame
4 weeks
Title
Schirmer's test (ST)
Description
The Schirmer test (ST) was performed using commercially available prepackaged sterile paper strips without anesthesia. The rounded bulb end of the strip was folded and placed in the lateral canthus away from the cornea and left in place for 5 minutes after which the wet strip length was recorded in mm. Tear deficiency is defined if ST is less than 5 mm wetting of the paper after 5 minutes.
Time Frame
4 weeks
Title
Meibum quality and expressibility.
Description
Meibum quality is assessed by applying the pressure on each of 8 glands of the central third of the lower lid on a scale of 0 to 3 for each gland: 0, clear; 1, cloudy; 2, cloudy with debris (granular); and 3, thick, like toothpaste (total score range, 0-24). Higher score indicates the higher severity of meibomian gland dysfunction.
Expressibility is assessed on a scale of 0 to 3 in five glands in the lower or upper lid, according to the number of glands expressible: 0, all glands; 1, three to four glands; 2, one to two glands; and 3, no glands. Higher score indicates the higher severity of meibomian gland dysfunction.
Time Frame
4 weeks
Title
Number of patients with ocular adverse events
Description
All ocular adverse events will be recorded throughout the study.
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 18 to less than 75 years.
Have OSDI scores ≥ 23 or Oxford staining grade ≥ 2.
Do not have following conditions:
Uncontrolled systemic diseases, active infection, advanced cancer. Pregnant and nursing women. • Have not recently used the following medications/interventions/surgery: Anticoagulants or anti-platelets. Topical undiluted blood products within 3 months. Punctal plug or contact lenses. Ocular surgery within 6 months.
Do not have active ocular infection/inflammation, abnormal eyelid function or severe meibomian gland dysfunction (MGD stage 4).
Have no contraindication for blood donations:
Positive human immunodeficiency virus, hepatitis B or C, or syphilis. Anemia (Hb < 11 g/dL) or platelet concentration < 150,000/ml.
Being able to stop current dry eye treatment for 48 hours before staring trial intervention
Willing to comply with the 4-week study protocol and provide informed consent.
Exclusion Criteria:
• None
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ammarin Thakkinstian, Ph.D.
Organizational Affiliation
Department of Clinical Epidemiology and Biostatistics, Mahidol University, Thailand
Official's Role
Study Director
Facility Information:
Facility Name
Ophthalmology Department, Ramathibodi Hospital
City
Ratchathewi
State/Province
Bangkok
ZIP/Postal Code
10400
Country
Thailand
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Data will be available upon the specific request.
Citations:
PubMed Identifier
34193498
Citation
Jongkhajornpong P, Numthavaj P, Anothaisintawee T, Lekhanont K, McKay G, Attia J, Thakkinstian A. Comparison of treatment efficacy between 100% platelet-rich plasma and 100% serum eye drops in moderate-to-severe dry eye disease: a randomised controlled trial protocol. BMJ Open. 2021 Jun 30;11(6):e048479. doi: 10.1136/bmjopen-2020-048479.
Results Reference
derived
Learn more about this trial
Comparison of Efficacy Between 100% Platelet-rich Plasma and 100% Serum Eye Drops in Dry Eye Disease
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