Evaluation of the Efficacy of 2% Cyclosporine in Preventing Graft Rejection

Aim/ Objective: Study consists of 2 separate and distinct entities A. Evaluation of the efficacy of 2% cyclosporine in preventing graft rejection in primary grafts w/o high risk characteristics study 1 (PKP study) B. Evaluation of the efficacy of 2% cyclosporine in preventing graft rejection in therapeutic keratoplasty- study 2(TKP study) Materials & Methods: In both arms Patients requiring keratoplasty, above the age of 18 whom satisfactorily meet The inclusion criteria are different for each study Eligible candidates will be enrolled after signing an Informed Consent form Patients will be randomized into one of 2 groups

• Only on topical steroids group A

• On topical steroids + 2% cyclosporine Group B Study design: Prospective, randomized non-blinded study at a single centre. Methodology In both arms

  1. Schedule of topical steroid administration : 6 times for 2 weeks; 5 times for 2 weeks; 4 times for a month; 3 times for a month, and, subsequently twice-a-day until 1 year is completed Systemic steroids may be administered in the initial 2 weeks at the discretion of the investigators. (For all patients with fungal keratitis topical steroids can preferrably be administered only after 2 weeks post keratoplasty.) Until then voveran ophtha may be used

  3. Patients randomized to receive 2% cyclosporine will receive the same 3 times a day for 2years

  4. All patients will be followed for a minimum period of 2 years

  5. Follow up schedule - at 1 week, 2 weeks, 1 month, 2 months, 3 months, then every 3 months until 2 years are completed

  6. All episodes of graft rejection will be treated as per accepted norms and the patient will no longer follow the standardized protocol for steroid administration

Study Overview

• Status: Unknown
• Conditions: Corneal Graft Rejection
• Intervention / Treatment: Drug: Prednisolone acetate1%,; Drug: Prednisolone acetate1%, cyclosporine 2%

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Tamil Nadu
    • Coimbatore, Tamil Nadu, India, 641014
      • Recruiting
      • Dr.Anita Raghavan
      • Contact: Dr.Anita Raghavan; Phone Number: 407 04224360400; Email: annieram2001@yahoo.com
      • Principal Investigator: Dr.Anita Raghavan
      • Sub-Investigator: Dr.Revathi Rajaraman
      • Sub-Investigator: Dr.Mangala Periyasamy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• FOR ARM 1

Age greater than 18 years

Vision more than 6/60 in the fellow eye.

No prior keratoplasty

Not more than 1 quadrant of corneal vascularisation

No peripheral anterior synechiae.

No active ocular surface disease (VKC, dry eye,)

Uncontrolled uveitis or glaucoma

No limbal stem cell failure.

No Prior h/o HSV

Primarily patients with dystrophies, degenerations and pseudophakic bullous keratopathy and non vascularised non herpetic corneal scars will be enrolled

ARM 2:

Inclusion criteria as above &

Those patients with medically unresponsive keratitis with no limbal involvement and in whom the graft size can be restricted to less than 9mm will be included in the study. This is to ensure that postoperative issues such as synechiae, recurrence of infection and uncontrolled glaucoma do not affect the study. Grafts must also be clear at the end of one month after surgery for patients to continue in the study..

Expected Outcome

1. Incidence of graft rejection in both arms.
2. secondary outcome Recovery from graft rejection in both arms.
3. Secondary outcomes- incidence of glaucoma and cataract.
4. secondary outcome Incidence of graft rejection in patients maintained only on cyclosporine after 1year.
5. It is expected that patients receiving cyclosporine will have a lesser incidence of graft rejection and exhibit faster recovery. The efficacy of long term prophylaxis of only cyclosporine in preventing graft rejection will also be evaluated.

Exclusion Criteria:Any condition that would increase the risk of non-rejection graft failure such as Stevens-Johnson syndrome, xerophthalmia or severe exposure keratitis. Schirmer's test ≤ 5 mm in 1 minute Clinical evidence of limbal stem cell deficiency History of or active herpes simplex virus keratitis or other acute corneal infection

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: penetrating keratoplasty; each arm will have two groups A and B.. Only on topical steroids(prednisolone acetate1%) group A On topical steroids + 2% cyclosporine Group B . Methodology of drug administration In both agroups 1. Schedule of topical steroid administration : 6 times for 2 weeks; 5 times for 2 weeks; 4 times for a month; 3 times for a month, and, subsequently twice-a-day until 1 year is completed . Topical steroids will be withdrawn at the end of ine year.Systemic steroids may be administered in the initial 2 weeks at the discretion of the investigators. 3. Patients randomized to receive 2% cyclosporine will receive the same 3 times a day for 2years .	Drug: Prednisolone acetate1%,; efficacy of prednisolone acetate1%alone versus prednisolone acetate 1%and cyclosporine 2% in preventing graft rejection; Other Names: pred forte (Prednisolone acetate1% ); Drug: Prednisolone acetate1%, cyclosporine 2%; penetrating keratoplasty--efficacy of prednisolone acetate1%alone versus prednisolone acetate 1%and cyclosporine 2% in preventing graft rejection; Other Names: pred forte (Prednisolone acetate1% ); aurosporine (cyclosporine 2%)
Active Comparator: therapeutic keratoplasty; each arm will have two groups A and B.. Only on topical steroids(prednisolone acetate1%) group A On topical steroids + 2% cyclosporine Group B . Methodology of drug administration In both agroups 1. Schedule of topical steroid administration : 6 times for 2 weeks; 5 times for 2 weeks; 4 times for a month; 3 times for a month, and, subsequently twice-a-day until 1 year is completed . Topical steroids will be withdrawn at the end of ine year.Systemic steroids may be administered in the initial 2 weeks at the discretion of the investigators. (For all patients with fungal keratitis topical steroids will be administered only after 2 weeks post keratoplasty.) Until then diclofenac sodium0.1% may be used 3. Patients randomized to receive 2% cyclosporine will receive the same 3 times a day for 2years .	Drug: Prednisolone acetate1%,; efficacy of prednisolone acetate1%alone versus prednisolone acetate 1%and cyclosporine 2% in preventing graft rejection; Other Names: pred forte (Prednisolone acetate1% ); Drug: Prednisolone acetate1%, cyclosporine 2%; penetrating keratoplasty--efficacy of prednisolone acetate1%alone versus prednisolone acetate 1%and cyclosporine 2% in preventing graft rejection; Other Names: pred forte (Prednisolone acetate1% ); aurosporine (cyclosporine 2%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
graft rejection	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recovery from graft rejection		5 years
Incidence of graft rejection in patients maintained only on cyclosporine after 1year	.graft rejection in patients only on cyclosporine 2% eye drops in the second year of study	5 years

Other Outcome Measures

Outcome Measure	Time Frame
incidence of glaucoma and cataract.	5 years

Collaborators and Investigators

• Sponsor: Aravind Eye Care System
• Investigators: Principal Investigator: Dr.Anita Raghavan, Medical Cornea Consultant

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: July 31, 2014
• First Submitted That Met QC Criteria: July 31, 2014
• First Posted (Estimate): August 1, 2014

Study Record Updates

• Last Update Posted (Estimate): August 1, 2014
• Last Update Submitted That Met QC Criteria: July 31, 2014
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Cyclosporine; Cyclosporins
• Other Study ID Numbers: IRB2011011CLI