Comparison of Efficacy Between 100% Platelet-rich Plasma and 100% Serum Eye Drops in Dry Eye Disease

Dry Eye Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04683796
• Other study ID #: 1996
• Status: Completed
• Phase: Phase 3
• Start date: February 1, 2021
• Est. completion date: March 30, 2023

Study information

• Verified date: October 2023
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: March 30, 2023
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Dry Eye Disease
• Dry Eye Syndromes
• Eye Diseases
• Keratoconjunctivitis Sicca

Intervention

Drug:
• 100% Autologous platelet rich plasma
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.
• 100% Autologous serum
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.

Locations

Country	Name	City	State
Thailand	Ophthalmology Department, Ramathibodi Hospital	Ratchathewi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	4 weeks
Primary	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.	4 weeks
Secondary	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.	4 weeks
Secondary	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.	4 weeks
Secondary	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.	4 weeks
Secondary	Number of patients with ocular adverse events	All ocular adverse events will be recorded throughout the study.	4 weeks