Intravitreal tPA and C3F8 for the Treatment of Submacular Haemorrhage as a Complication of Neovascular AMD

NCT01835067 | Completed Phase 2

• 1 other identifier: EudraCT Number: 2012-004078-24
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 5

Brief Summary

This study will recruit patients who have recently had a submacular haemorrhage (bleed under the part of the retina responsible for detailed vision), as a complication of wet age-related macular degeneration (wet AMD). Wet AMD is a very common disease where abnormal blood vessels form under the retina and leak, causing a significant reduction in vision. The study will investigate treatment of the bleed with various combinations of the two drugs: tissue plasminogen activator (tPA) - designed to dissolve the blood clot; and perfluoropropane (C3F8) - designed to shift the blood clot away from the central part of the retina (the macula). tPA is a commonly used 'clot-buster' drug for the treatment of stroke. C3F8 is a gas commonly used in eye surgery. Patients recruited will be divided into four groups: control group that receive none of the above drugs; one group that receives only tPA; one group that receives only C3F8; and one group that receives both. All patients will receive the current gold standard treatment for wet AMD, ranibizumab (Lucentis®). The aim of the study is to improve vision in a condition, which left untreated, would cause severe visual loss.

Conditions

Exudative Macular Degeneration; Retinal Hemorrhage

Keywords

Macular degeneration; Submacular haemorrhage

Outcome Measures

Primary Outcomes (1)

• Mean ETDRS visual acuity

  3 months

Secondary Outcomes (7)

• Mean ETDRS visual acuity

  1 and 12 months

• Percentage patients 15 letters or greater improvement in ETDRS visual acuity

  12 months

• Percentage patients 0 letters or greater improvement in ETDRS visual acuity

  12 months

• Percentage patients 15 letters or greater loss in ETDRS visual acuity

  12 months

• Mean total area of macular haemorrhage on colour fundus photography

  1, 3 and 6 months

Study Arms (4)

Control Group (A)

SHAM COMPARATOR

Ranibizumab only (active control). Participants will receive a 'sham injection' to simulate C3F8 and/or tPA administration.

Drug: Ranibizumab

C3F8 Only Group (B)

EXPERIMENTAL

C3F8 given. Ranibizumab given as standard.

Drug: Ranibizumab; Drug: C3F8 Gas

tPA and C3F8 Group (C)

EXPERIMENTAL

Both C3F8 gas and tPA given. Ranibizumab given as standard.

Drug: Ranibizumab; Drug: C3F8 Gas; Drug: tPA

tPA Only Group (D)

EXPERIMENTAL

tPA given. Ranibizumab given as standard.

Drug: Ranibizumab; Drug: tPA

Interventions

Ranibizumab DRUG

Single intravitreal injection of 500 micrograms ranibizumab in 0.05mls

Also known as: Lucentis®

C3F8 Only Group (B); Control Group (A); tPA Only Group (D); tPA and C3F8 Group (C)

C3F8 Gas DRUG

Single intravitreal injection of 0.3 mls C3F8

Also known as: Perfluoropropane, Perflutren, Octafluoropropane

C3F8 Only Group (B); tPA and C3F8 Group (C)

tPA DRUG

Single intravitreal injection of 50 micrograms tPA in 0.05 mls

Also known as: tissue plasminogen activator, alteplase, Actilyse®

tPA Only Group (D); tPA and C3F8 Group (C)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults of either sex aged 50 years and older;
• SMH associated with treatment-naive or previously treated wet AMD, including retinal angiomatous proliferation (RAP) and idiopathic polypoidal choroidal vasculopathy (IPCV);
• SMH of at least 1 disc area, involving the fovea, and of sufficient density to obscure RPE detail;

You may not qualify if:

• SMH that is known to have been present for greater than 2 weeks duration, as evidenced by history, pre-trial documentation, or fundus appearance;
• Presence of significant vitreous haemorrhage precluding accurate retinal assessment in the study eye;
• Diabetic maculopathy in the study eye;
• Visually significant cataract in the study eye;
• Amblyopia in the study eye;
• Presence of other ocular disease causing concurrent vision loss in the study eye;
• Advanced glaucoma in the study eye (cup-to-disc ratio greater than 0.8);
• Pregnant and or lactating women;
• Women of childbearing potential including those who are not sterilised or at least one year post menopausal;
• Participation in a clinical interventional trial in the preceding 6 months;
• Documented evidence of a visual acuity less than 25 ETDRS letters at three consecutive visits in the study eye, prior to the onset of submacular haemorrhage;
• Participants who are known to have been ineligible for NICE approved ranibizumab therapy prior to the development of the SMH;
• Current treatment for wet age-related macular degeneration with an intravitreal agent other than ranibizumab, bevacizumab or aflibercept;
• Patients who, in the opinion of the Investigator, would not be willing or able to comply with the study protocol, including posturing requirements.
• Patients who show insufficient understanding of the clinical trial or treatment options.

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead

Study Sites (5)

Maidstone Hospital

Maidstone, Kent, ME16 9QQ, United Kingdom

Location

Sunderland Eye Infimary

Sunderland, Tyne and Wear, SR2 9HP, United Kingdom

Location

Hull & East Yorkshire Hospital NHS Trust

Hull, HU3 2JZ, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Southend University Hospital NHS Foundation Trust

Southend, SS0 0RY, United Kingdom

Location

Related Publications (1)

• Murphy GSP, Saleh A, Ayis S, Cheema MR, Mehta A, Steel DH, Membrey L, Costen M, Jackson TL. Tissue Plasminogen Activator or Perfluoropropane for Submacular Hemorrhage in Age-Related Macular Degeneration: A Factorial Randomized Clinical Trial. JAMA Ophthalmol. 2024 Dec 1;142(12):1157-1164. doi: 10.1001/jamaophthalmol.2024.4297.

  PMID: 39418015 DERIVED

MeSH Terms

Conditions

Wet Macular Degeneration; Retinal Hemorrhage; Macular Degeneration

Interventions

Ranibizumab; perflutren; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Eye Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Biological Factors

Study Officials

• Timothy L Jackson, PhD,FRCOpht

  King's College Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2013
• First Posted: April 18, 2013
• Study Start: September 1, 2014
• Primary Completion: November 1, 2019
• Study Completion: December 1, 2019
• Last Updated: July 14, 2020

Record last verified: 2020-02

Locations

GB (5)