We have aimed to evaluate the efficacy of using oral Doxycycline on the number of intravitreal Bevacizumab injection, macular thickness and volume and visual acuity in diabetic patients with clinically significant macular edema (CSME).
Design
Phase 3 randomized controlled trial on 60 diabetic patients with CSME, enrolled between November 2018 and February 2019, receiving intervention for 4 months and then followed for 6 months.
Settings and conduct
Patients referred to the ophthalmology clinic of Imam Khomeini
Hospital in Ahvaz were randomly divided into two equal groups.
Fluorescence angiography was performed at the first visit. Pre and post-treatment changes in optical parameters including BCVA
(Log MAR), CMT (µm) and macular volume (mm3
) in optical coherence tomography (OCT) were assessed.
Participants/Inclusion and exclusion criteria
Inclusion criteria:
Diabetic patients with confirmed Clinically Significant Macular Edema
Exclusion criteria:
Patients with previous history of surgery for retinal detachment
Patients with glaucoma
Patients with uveitis
Patients with macular geographic atrophy
Patients with macular scar
Patients with gastrointestinal distress
Intervention groups
Patients were randomly divided into two equal groups; Group A receiving 1.25 mg bevacizumab (Avastin, Genetech Co, San Francisco, USA) IV injection and group B receiving 1.25 mg IV injection of bevacizumab along with oral doxycycline (200 mg per day) (Hakim Pharmaceutical Co, Iran) for 4 months. Subsequently, all patients in both groups were followed up for 6 months.
Main outcome variables
Changes in central macular thickness and volume
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200720048150N1
Registration date:2020-10-28, 1399/08/07
Registration timing:retrospective
Last update:2020-10-28, 1399/08/07
Update count:0
Registration date
2020-10-28, 1399/08/07
Registrant information
Name
Ebrahim Azizi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 31 3336 4686
Email address
eazizi324@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2018-10-23, 1397/08/01
Expected recruitment end date
2019-01-20, 1397/10/30
Actual recruitment start date
2018-11-22, 1397/09/01
Actual recruitment end date
2019-02-21, 1397/12/02
Trial completion date
2020-02-15, 1398/11/26
Scientific title
The efficacy of using oral doxycycline with intravitreal Bevacizumab injection in diabetic patients with clinically significant macular edema
Public title
The efficacy of oral doxycycline with Bevacizumab in diabetes
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Diabetic patients with confirmed Clinically Significant Macular Edema
Exclusion criteria:
Patients with previous history of surgery for retinal detachment
Patients with glaucoma
Patients with uveitis
Patients with macular geographic atrophy
Patients with macular scar
Patients with gastrointestinal distress
Age
No age limit
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
60
Actual sample size reached:
60
Randomization (investigator's opinion)
Randomized
Randomization description
The randomization was performed using the online software www.random.org. The random sequence of numbers was generated by a researcher external to the study team and concealment of the allocation was assured until the moment of the intervention, stored in opaque envelopes. The patients were allocated to the intervention group (IG) or to the control group (CG) by a researcher who did not apply the intervention or evaluated the outcomes. Intervention group: patients received 1.25 mg IV injection of bevacizumab (Avastin, Genetech Co, San Francisco, USA) along with oral doxycycline (200 mg per day) (Hakim Pharmaceutical Co, Iran) for 4 months. Control group: control group received 1.25 mg bevacizumab (Avastin, Genetech Co, San Francisco, USA) IV injection.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethical committee of Ahvaz University of Medical Sciences
Street address
International Affairs Office, Ahvaz Jundishapur University of Medical Sciences, Golestan St. , Ahvaz , Iran
City
Ahvaz
Province
Khouzestan
Postal code
15794- 61357
Approval date
2019-03-16, 1397/12/25
Ethics committee reference number
IR.AJUMS.REC.1397.932
Health conditions studied
1
Description of health condition studied
Diabetes, Clinically significant macular edema
ICD-10 code
E11.3
ICD-10 code description
Type 2 diabetes mellitus with ophthalmic complications
2
Description of health condition studied
Diabetes, Clinically significant macular edema
ICD-10 code
E10.3
ICD-10 code description
Type 1 diabetes mellitus with ophthalmic complications
Primary outcomes
1
Description
Central macular thickness
Timepoint
Before intervention and 2, 4, 6 and 9 months after intervention
Method of measurement
Optical Coherence Tomography images were generated using the Fast Macular Thickness Scan consisting of six radial scans oriented 30 degrees from one another, each having a 2 mm axial depth and 6 mm transverse length. Each image had 10 μm axial and 20 μm transverse resolutions in tissue and consisted of 1024 axial pixels by 512 transverse pixels with a maximum scan velocity of 400 axial per second.
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: patients received 1.25 mg IV injection of bevacizumab (Avastin, Genetech Co, San Francisco, USA) along with oral doxycycline (200 mg per day) (Hakim Pharmaceutical Co, Iran) for 4 months.
Category
Treatment - Drugs
2
Description
Control group: control group received 1.25 mg bevacizumab (Avastin, Genetech Co, San Francisco, USA) IV injection.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences
Full name of responsible person
Ali Kasiri
Street address
Department of Ophthalmology, Faculty of Medicine, Infectious Ophthalmic Research Center, Ahvaz Jundishapur University of Medical Sciences, Golestan street, Ahvaz
City
Ahvaz
Province
Khouzestan
Postal code
15794- 61357
Phone
+98 61 3333 9196
Fax
Email
Kasiri-a@ajums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Ali Kasiri
Street address
Department of Ophthalmology, Faculty of Medicine, Infectious Ophthalmic Research Center, Ahvaz Jundishapur University of Medical Sciences, Golestan street, Ahvaz
City
Ahvaz
Province
Khouzestan
Postal code
15794- 61357
Phone
+98 61 3333 9196
Email
Kasiri-a@ajums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Ahvaz University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
2
Sponsor
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Mohammad Badavi
Street address
Vice Chancellor for Research and Technology, Ahvaz medical university of science
City
Ahvaz
Province
Khouzestan
Postal code
۶۱۳۴۹-۳۷۳۳۳
Phone
+98 61 3336 2414
Email
eazizi324@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Ahvaz University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Ali Kasiri
Position
Assistant Professor
Latest degree
Subspecialist
Other areas of specialty/work
Ophthalmology
Street address
Department of Ophthalmology, Faculty of Medicine, Infectious Ophthalmic Research Center, Ahvaz Jundishapur University of Medical Sciences, Golestan street, Ahvaz
City
Ahvaz
Province
Khouzestan
Postal code
15794- 61357
Phone
0098 33339196
Email
Kasiri-a@ajums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Ali Kasiri
Position
Assistant Professor
Latest degree
Subspecialist
Other areas of specialty/work
Ophthalmology
Street address
Department of Ophthalmology, Faculty of Medicine, Infectious Ophthalmic Research Center, Ahvaz Jundishapur University of Medical Sciences, Golestan street, Ahvaz
City
Ahvaz
Province
Khouzestan
Postal code
15794- 61357
Phone
0098 33339196
Email
Kasiri-a@ajums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Ali Kasiri
Position
Assistant Professor
Latest degree
Subspecialist
Other areas of specialty/work
Ophthalmology
Street address
Department of Ophthalmology, Faculty of Medicine, Infectious Ophthalmic Research Center, Ahvaz Jundishapur University of Medical Sciences, Golestan street, Ahvaz
City
Ahvaz
Province
Khouzestan
Postal code
15794- 61357
Phone
0098 33339196
Email
Kasiri-a@ajums.ac.ir
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Yes - There is a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
All individual participant data (IPD) consisting patient's general characteristics, efficacy of treatment and final conclusion are accessible for applicants
When the data will become available and for how long
All individual participant data (IPD) have been accessible for applicants from 5th June 2020
To whom data/document is available
Data products from this study will be made available without cost to researchers and analysts.
Under which criteria data/document could be used
Data will be made accessible through a public email (Kasiri-a@ajums.ac.ir) that allows querying as has been set up for a similar project.
From where data/document is obtainable
Applicants should send email to responsible person (Kasiri-a@ajums.ac.ir).
What processes are involved for a request to access data/document
Users must agree to the conditions of use governing access to the public release data, including restrictions against attempting to identify study participants, destruction of the data after analysis is completed, reporting responsibilities.