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Age-related Macular DegenerationPhase 4RATENCT01319188

Ranibizumab and the Risk of Arterial Thromboembolic Events

A Phase 4 study testing 0.5 mg of ranibizumab and 0.5 mg of ranibizumab + photodynamic therapy in people with Age-related Macular Degeneration and Coronary Artery Disease, run by Ural State Medical University at 2 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The investigators assume that ranibizumab might be dangerous in patients with history of coronary artery disease or cerebrovascular events. The main objective of study is to reveal contraindications for ranibizumab prescription in patients with history of coronary artery disease and cerebrovascular events. Read more about this study

Who is it for?
Ages 50 to 90 yearsHealthy volunteers can take part
What is being tested?
0.5 mg of ranibizumab and 0.5 mg of ranibizumab + photodynamic therapy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
380 participants
Where
2 sitesin 2 countries
Study dates
Jun 2010to Apr 2015
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 90 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • age - 50 years old and older
  • male and female
  • age-related macular degeneration (AMD)
  • have a lesion in the study eye with a total size of less than 12 optic disc areas for minimally classic or occult lesions but no more than 5400 μm in greatest linear dimension for predominantly classic lesions
  • have best corrected visual acuity of 6/12 to approximately 6/96 (Snellen equivalent), assessed with the use of charts from the Early Treatment Diabetic Retinopathy Study (ETDRS) (70 to 25 ETDRS 1 m equivalent letter scores; patients initially view the charts at a starting distance of 4 m, the number of correctly read letters are given a correction factor with the final letter score being the equivalent of a patient reading it at 1m. A score of 55 letters approximates to 6/24 Snellen acuity)
  • have no permanent structural damage to the central fovea
  • have had no previous treatment for exudative age related macular degeneration
  • healthy subjects (no history of cardio- or cerebrovascular events), or history of coronary artery disease (cardiovascular events - myocardial infarction, unstable angina), or history of cerebrovascular events (brain ischemia, and/or stroke), but not in the preceding six months

Who cannot join

  • history of cardiovascular events (myocardial infarction, unstable angina) or cerebrovascular events in the preceding six months
  • stenting, or any surgery in the preceding six months
  • other acute illnesses in the preceding three months
  • III-IV NYHA functional class of heart failure
  • mental and brain disorders
  • pregnancy
Show all 10Show fewer
  • family hypercholesterolemia
  • blood disorders
  • malignant tumors
  • participation to any drug investigation during the previous three months

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Netherlands1 site

  • De Haar Research Foundation

    Rotterdam, South Holland, 3071PR

Other trials in Netherlands

Russia1 site

  • Ural Institute of Cardiology

    Yekaterinburg, 620144

Other trials in Russia

About this study

Official title: Ranibizumab for Age-Related Macular Degeneration and the Risk of Arterial Thromboembolic Events (RATE)

The investigators assume that ranibizumab might be dangerous in patients with history of coronary artery disease or cerebrovascular events. The main objective of study is to reveal contraindications for ranibizumab prescription in patients with history of coronary artery disease and cerebrovascular events. Moreover, an association between management with ranibizumab and ATE rate in healthy above 50 years old persons is a concern of great interest as well.

Read the detailed description

Age-related macular degeneration (AMD) is a degenerative condition affecting the macula or central area of the retina in elderly people. Early AMD is marked by the presence of soft drusen and/or retinal pigment abnormality (hyper- and hypopigmentation). Late AMD includes 2 forms, nonneovascular (dry) AMD and neovascular (wet) AMD. Despite new medical and surgical interventions, AMD remains a leading cause of vision loss in elderly people all over the world.

Ranibizumab is one of the most effective approaches of AMD management. Ranibizumab - a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A (VEGF A) - has been evaluated for the treatment of AMD. Ranibizumab binds to the receptor binding site of active forms of VEGF-A. VEGF-A cause neovascularization and leakage in models of ocular angiogenesis and vascular occlusion, and is thought to contribute to the progression of neovascular AMD and macular edema following RVO. Prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.

There have been a number of studies that have examined a possible association between ranibizumab and arterial thromboembolic events (ATE). The ATE rate in the three controlled neovascular AMD studies during the first year was 1.9% (17 out of 874; 0.3-0.5 mg LUCENTIS) vs 1.1% (5 out of 441) in control arms (AMD-1, AMD-2). In the second year the ATE rate was 2.6% (1323 patients; Lucentis 879) vs Control 444 (p < 0.05). The ATE rate in the two controlled RVO studies (RVO-1, RVO-2) during the first six months was 0.8% (789 patients; Lucentis 527 vs Sham 262).

The investigators assume that ranibizumab can be rather dangerous in patients with history of coronary artery disease or cerebrovascular events. The main objective of study is to reveal contraindications for ranibizumab prescription in patients with history of coronary artery disease and cerebrovascular events. Moreover, an association between management with ranibizumab and ATE rate in healthy above 50 years old persons is a concern of great interest as well.

Being tested
0.5 mg of ranibizumab, 0.5 mg of ranibizumab + photodynamic therapy, Sham injection
Keywords
Age-related macular degeneration, ranibizumab, acute thromboembolic events, coronary artery disease, cerebrovascular disease
Medical subject headings
Macular Degeneration, Coronary Artery Disease, Cerebrovascular Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 0.5 mg of ranibizumabDrug

    Also called Lucentis

    Intravitreous ranibizumab (0.5 mg, injections at four week intervals for six months followed by further treatment at three month intervals with total duration of treatment until 24 months).

  • 0.5 mg of ranibizumab + photodynamic therapyProcedure or surgery

    Also called Lucentis + laser therapy

    Photodynamic treatment with ranibizumab for predominantly classic type neovascular age related macular degeneration.

  • Sham injectionOther

    Also called Sham comparator

    Sham treatment for occult or minimally classic type neovascular age related macular degeneration.

Study groups in NCT01319188
Study groupRoleWhat they receive
0.5 mg of ranibizumabActive comparatorNot described
Receives: Drug: 0.5 mg of ranibizumab
injection + photodynamic therapyActive comparatorNot described
Receives: Procedure: 0.5 mg of ranibizumab + photodynamic therapy
Sham injectionSham comparatorNot described
Receives: Other: Sham injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Arterial thromboembolic events rate

    This is a combined primary outcome that included:

    • all cause mortality
    • nonfatal stroke
    • nonfatal myocardial infarction
    • vascular death

    Measured: at month 6, 12 and 24

Secondary outcomes (11)

  1. Serum concentration of ranibizumab

    Serum concentration of ranibizumab

    Measured: at month 6, 12 and 24

  2. Serum VEGF

    Measurement of serum VEGF

    Measured: at month 6, 12 and 24

  3. Mean change in visual acuity (letters)

    mean change in visual acuity (letters)

    Measured: at month 6, 12 an 24

  4. Coronary and/or cerebral stenting, and/or CABG rate

    Coronary and/or cerebral stenting, and/or CABG rate

    Measured: at month 6, 12 an 24

  5. Total cholesterol

    Total cholesterol measurement

    Measured: at month 6, 12 and 24

  6. Systolic blood pressure

    Systolic blood pressure

    Measured: at month 6, 12 and 24

  7. NYHA (New York Heart Association) functional class of heart failure

    NYHA (New York Heart Association) functional class of heart failure

    Measured: at month 6, 12 and 24

  8. Diabetes mellitus morbidity

    Diabetes mellitus morbidity

    Measured: at month 6, 12 and 24

  9. Serum fibrinogen

    Serum fibrinogen measurements

    Measured: at month 6, 12 and 24

  10. Serum C-RP

    Serum C-RP measurements

    Measured: at month 6, 12 and 24

  11. Serum D-dimer

    Serum D-dimer measurements

    Measured: at month 6, 12 and 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2011 (estimated)
  2. Study startJun 2010
  3. Primary completionOct 2012
  4. Study completionApr 2015

Why it stopped: The study was terminated under the political pressure of the Federal Security Service of the Russian Federation (FSB) and the Russian Society of Cardiology

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Screening
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
380 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01319188
Sponsor's protocol ID
RATE01
Acronym
RATE
Status last verified
May 2015
First submitted
18 Mar 2011
Last updated
19 May 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing 0.5 mg of ranibizumab and 0.5 mg of ranibizumab + photodynamic therapy in people with Age-related Macular Degeneration and Coronary Artery Disease, run by Ural State Medical University at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated under the political pressure of the Federal Security Service of the Russian Federation (FSB) and the Russian Society of Cardiology). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Arterial thromboembolic events rate (time frame: at month 6, 12 and 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01319188.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2015.

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