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LUCAS (Lucentis Compared to Avastin Study)

2014-08-27 03:13:33 | BioPortfolio

Summary

Age-related macular degeneration (AMD) is the most common cause of blindness in individuals over 50 years of age. There has not been any effective treatment of the exudative form until recently. Bevacizumab and ranibizumab are two agents developed by the American pharmaceutical corporation Genentech, both of which inhibit blood vessel growth factors. These drugs, when injected intraocularly, reduce the pathological growth of blood vessels under the macula (the central area of the retina which is responsible for detailed vision). Bevacizumab (Avastin) is an antibody developed for intravenous treatment of metastasized colon cancer. Ranibizumab (Lucentis) is an antibody fragment developed from a similar antibody. It was introduced 2006 as an effective treatment for wet AMD. Treatment of wet AMD with Avastin has experimentally shown similar effects to ranibizumab, and has been used off-label in many countries, both before and after Lucentis received approval. Ranibizumab has, in controlled studies, been shown to be effective in improving vision in some patients, and to stop further visual loss in most patients. Treatment costs are, however, up to 50 times higher compared to use of bevacizumab, where a single vial can be used to prepare as many as 20 injections. Although the effects of Avastin have not been documented in large controlled studies, there are hundreds of articles published with regard to its effect and safety. Avastin has no formal approval for the indication AMD, but is used in many countries because of its effectiveness and low price. Such use has been criticized on the grounds of insufficient documentation. There is thus a recognized need for large randomized studies to garner proper scientific proof of Avastin's effectiveness regarding wet AMD.

This protocol describes such a randomized multicenter study, performed in Norway, comparing ranibizumab and bevacizumab use for AMD. The goal of the study is to demonstrate if the two agents are equivalent regarding both efficacy and safety. A total of 420 patients with objective evidence of wet AMD will be randomized to a double-blind treatment with ranibizumab or bevacizumab over the course of 2 years. The treatment interval will be determined by protocol called "inject and extend." The shortest interval will be 4 weeks and the longest 12 weeks. The goal of such a protocol is to determine an appropriate individual treatment regimen by gradually increasing the interval between injections. An extended interval between each examination and injection visit can reduce the burden upon an ophthalmology department, as well as increasing a patient's comfort. Such a protocol could also aid in reducing the risk of recurrence.

Description

LUCAS (LUcentis Compared to Avastin Study) A randomized, double-blind, prospective multicenter study comparing the effect of intravitreal injection of bevacizumab (Avastin) to ranibizumab (Lucentis) when given to patients with exudative (wet) age-related macular degeneration in Norway.

Version: 4, Protocol: 166-09, EudraCT: 2008-004225-41

Background:

Age-related macular degeneration (AMD) is the most common cause of blindness in individuals over 50 years of age. Previously available treatment modalities have shown limited efficacy, and the disease has generally led to a gradual loss of central vision in most affected patients.Dry AMD begins with yellowish inclusions within the macula lutea, the central area of the retina that provides us with detailed vision. These inclusions are called drusen and lie between the retina and the underlying choroidea. This can eventually lead to atrophy of macular tissue and thereby loss of photoreceptors, thus resulting in visual loss. There is still no effective treatment for this form of AMD, although use of a combination of antioxidants and vitamins has been shown to reduce the risk of progression to wet AMD. The wet form of AMD is characterized by pathological growth of choroidal blood vessels under the macula. These abnormal vessels leak fluid and proteins which in turn leads to scaring and loss of visual function. There has been no effective treatment for this process until recently. Previously available treatment modalities including photodynamic therapy (PDT) with verteporfin, as well as pegaptanib (Macugen) injections have been show to limit the loss of vision, but only a small percentage of those treated experience visual improvement.The etiology of AMD is not fully understood, but genetic factors clearly play a role. Growth factors for blood vessels play a significant role in the pathogenesis of wet AMD, especially the protein VEGF-A (Vascular Endothelial Growth Factor A). VEGF-A stimulates growth of new vessels and increases vessel permeability. Ranibizumab is a recombinant, humanized, monoclonal antibody that neutralizes all active forms of VEGF-A. This drug has been developed by Genentech, a pharmaceutical company based in California. It is marketed in Europe since 2006 by Novartis under the name Lucentis. It has been shown in controlled clinical studies that ranibizumab, when injected intravitreally monthly, can inhibit loss of visual acuity and improve vision for up to two years in patients with wet AMD(1). Bevacizumab is another pharmaceutical developed by Genentech. It is used for treatment of metastasized colon cancer, and is marketed under the name of Avastin by Hoffmann La Roche.Bevacizumab is a full length antibody with a molecular weight of 150 kDa, while ranibizumab is an antibody fragment with a molecular weight of 48 kDa. Both are derived from the same monoclonal murine antibody. Ranibizumab has been genetically modified to increase its affinity to the VEGF-A receptor. Bevacizumab has a longer half-life than ranibizumab. This is of interest as it may affect both its actions upon the targeted organ, as well as its systemic effects. Many retrospective and smaller prospective studies has shown an equivalent ocular clinical effect of these two drugs when given intravitreally as 0.05 ml Lucentis 10 mg/ml, or 0.05 ml Avastin 25 mg/ml (1, 2, 3, 7).The effects of Avastin upon wet AMD are not as yet documented in large controlled trials. There are, as mentioned, hundreds of publications detailing its effects and safety. Large scale controlled studies has been initiated in the USA (CATT), in the UK (IVAN) and in Germany (VIBERA). When compared to these, LUCAS is the only study where an "inject and extend" principle has been chosen. A driving motive behind the ocular use of Avastin is the highly significant difference in price between these two drugs (4, 6). A single dose of Lucentis cost 10,419 NOK (1,805 USD) as of December 2008. That translates to an annual cost of treatment of 10,419 to 125,028 NOK (1,805 to 21,680 USD) per patient. Avastin is sold in vials of 4 ml with a concentration of 25 mg/ml at a cost of 3,689 NOK (640 USD). Such a vial can theoretically be divided into 80 doses, but in practice 20 syringes can be prepared per vial for use the same day. The unit price of Avastin will therefore be determined by the number of issued treatments from a vial, but will range between 184 and 3,689 NOK (32 to 640 USD). The annual cost of treatment per patient will therefore lie between 184 and 44,268 NOK (32 to 7,663 USD).

Known Safety of Avastin:

There is widespread worldwide use of Avastin intravitreally for wet AMD, but also for other retinal vascular pathologies, such as those seen in conjunction with diabetes mellitus and retinal venous occlusions. There is great interest for studies of possible ocular and systemic side effects of Avastin. Although there is a lack of large prospective, randomized trials, there are many retrospective studies published. The Association for Research in Vision and Ophthalmology (ARVO) is the leading organization for research within ophthalmology. Over 200 papers pertaining to the effect and safety of ocular use of Avastin were presented at the annual ARVO meeting in Florida 2008.

VEGF (Vascular Endothelial Growth Factor) is known to have neurotropic effects, and has in animal models led to reduction of neuron damage in ischemic conditions. Both Avastin and Lucentis are anti-VEGF agents that block all VEGF isotypes. Considering this, studies have been performed to see Avastin's effect on the neurosensory retina. We are unaware of any publication showing toxicity. The Tübingen Bevacizumab Study Group examined retinal function measured at 4 months with EOG (ElectroOculoGram) and ERG (ElectroRetinoGram). No retinal toxicity was shown. The same study showed 1 year visual field results (Goldmann) with particular attention paid to possibly peripheral effects. The results showed stabile visual fields aside from small fluctuations (10).

As mentioned, there is much interested In determining possible systemic side effects of intravitreal Avastin use. The Australian "Blue Mountains Eye Study" has shown an increased risk for cardiovascular disease in individuals with AMD (11). There are well known systemic complications in conjunction with high-dose intravenous Avastin treatment of metastasized colon cancer. A meta-analysis of 5 randomized studies of intravenous Bevacizumab treatment of colorectal cancer has shown an increased incidence of arterial thromboembolic incidents (12). However, the quantity of Avastin when used systemically is approximately 840 times that which is used for an intravitreal injection (based on the example of a 70 kg patient receiving 15 mg/kg vs. an intravitreal dose of 1.25 mg).

"The International Intravitreal Bevacizumab Safety Survey" was published in July 2006 (13). 70 centers in 12 countries reported the results of 7,113 injections given to 5,228 patients between November 2005 and April 2006. The ocular complications were few: endophthalmitis (0.01 percent) and retinal detachment (0.04 percent). Systemic adverse events included: mild systemic hypertension (0.21 percent), TIA (0.01 percent), cerebrovascular accident (0.07 percent) and deep venous thrombosis (0.01 percent). There were no reported cases of myocardial infarction.The Pan-American Collaborative Retina Study Group (PACORES) published in August 2007 12 month retrospective safety data of 1.25 mg and 2.5 mg intravitreal dosage of Avastin (14). This study is based upon 4,303 injections in 1,310 eyes. The risk of ocular complications observed here were low as well: endophthalmitis (0.16 percent) and retinal detachment (0.02 percent). Systemic adverse events were also unusual: cerebrovascular accident (0.5 percent) and myocardial infarction (0.4 percent).We can thus conclude by stating that ophthalmological use of Avastin is considerable on a worldwide basis. Numerous studies indicate a low incidence of side effects. However, there have been no large prospective studies, and thus there is great both scientific and medical economic interest in producing such reports.

Purpose:

LUCAS is a prospective, randomized, multicenter study comparing the effects of intravitreal injection of bevacizumab (Avastin) with ranibizumab (Lucentis) when given to patients with exudative (wet) AMD in Norway.

The study will include 420 patients to be recruited starting March 2009. The study will thereafter continue for 2 years, with the final patient exams occurring by December 2012.

Design:

LUCAS is a multicenter, randomized, double-blind study, with 1:1 parallel groups treated with either bevacizumab (Avastin) 0.05 ml (25 mg/ml) or ranibizumab (Lucentis) 0,05 ml (10 mg/ml). The drug is injected intravitreally according to an "inject and extend" principle (5).

Randomization will be stratified by center and performed with minimization according to prognostic factors.

Treatment Regimen:

Bevacizumab (Avastin) will be given as an intravitreal injection of 0.05ml (25 mg/ml) from a vial containing 4 ml.

Ranibizumab (Lucentis) will be given as an intravitreal injection of 0.05 ml (10 mg/ml) from a vial containing 0.23 ml.

Follow-up and treatment will follow a principle called "inject and extend." This connotes the following: initial follow-up and injection with a 4 week intervals until the macula is dry. When dry, then follow-up and injection will be increased 2 weeks at a time. If the patient has a recurrence of wet AMD, then the interval is reduced by 2 weeks at a time until the macula is once again dry. The shortest interval is 4 weeks. When once again extending, the treatment interval shall not be as long as the interval of the original recurrence, as this could confer risk for new activity. Therefore further follow-up and injection occurs at the "ideal" interval which is hereby defined as being 2 weeks less than that of the original recurrence. With this method, the patient receives an injection at each follow-up, presuming that no complications occur. The maximum interval is limited to 12 weeks. Treatment will continue for 2 years. After the study is completed, then the patient is to be offered continued treatment, in accordance with the ophthalmology department's routines, If there is no response to treatment after 3 injections with a 4 week interval, then the patient shall be removed from the study and be offered alternative treatment, such as combination treatment with photodynamic therapy (PDT).

Baseline:

All required examinations and tests that are included in the baseline visit must have been completed no longer than 7 days before randomization. If the any of these exams are older than 7 days, then they must be repeated. The informed consent form must be signed before proceeding with these examinations and tests.

Blood tests to be taken after overnight fasting and before the first injection:

Hemoglobin, white blood cell count, platelet count, blood differential, creatinine, total cholesterol, HDL-cholesterol and triglycerides.

The results of these blood tests are to be sent masked and marked with the patient ID-number to Karina Berg, MD; Dept. of Ophthalmology; Oslo University Hospital HF, Ullevål; 0407 Oslo.

Blood pressure must be measured, and this before introducing a catheter for fluorescein angiography (FA).

Blood pressure is to be measured with the patient seated after 5 minutes of rest. Consecutive measurements throughout the study should, if possible, be made on the same arm.

Visual acuity must be measured using the ETDRS protocol (chart at 4 meters) before pupil dilation.

Fundus photography and fluorescein angiography (FA) may be performed at the screening examination if that is within a week before the baseline examination.

Fundus photography and FA of both eyes is to be performed in mydriasis. Images shall include the entire lesion. FA: Start by capturing images from the study eye as early as possible, e.g. 0, 10, 15, 20, 30 seconds, 1 min, 1.5 min, 2 min, 5 min and the final image at 10 minutes. If it is appropriate to acquire images from the non-study eye: the first images should be captured before 1 minute, e.g. 40-45 s, 1:15 min, 2 min, 5 min and the final image at 10 minutes.

Fundus and FA images are to be sent masked and marked with the patient ID-number to Karina Berg, MD; Dept. of Ophthalmology; Oslo University Hospital HF, Ulleval, 0407 Oslo.

Optical Coherence Tomography (OCT)of both eyes is to be performed in mydriasis.

The manufacturer of the OCT apparatus may vary between centers, but the following applies to the Zeiss Stratus OCT:

"Macular thickness map" is to be performed for a qualitative evaluation of macular morphology.

"Fast macular thickness map" is to be performed for determination of central macular thickness.

Examination by the ophthalmologist.Inclusion and exclusion criteria are evaluated.A patient history is taken including other somatic diseases, and relevant medications are noted.Intraocular pressure is measured and then an examination in mydriasis is performed.The patient is recruited for participation into the study.The patient is randomized into one of the treatment groups. The patient is given a patient ID-number which shall be used in all study documentation, photographs and OCT-exams.The patient receives an intravitreal injection in the study eye with either Avastin or Lucentis in accordance with the results of the randomization.

Follow-up:

All patients will be followed for 2 years. Examinations and injections will be executed in accordance to the herein explained "inject and extend" protocol.

Blood pressure and pulse is to be measured by a nurse at each exam. Visual acuity (VA) is to be measured with the ETDRS-chart by a nurse at each exam. A new refraction is to be performed at 1 year and again at 2 years.

OCT is to be performed at each exam.

The following applies to the Zeiss Stratus OCT:

"Macular thickness map" is to be performed for a qualitative evaluation of macular morphology.

"Fast macular thickness map" is to be performed for determination of central macular thickness.

Fundus photography and fluorescein angiography (FA) FA is to be performed annually, but in addition may be performed as needed in order to evaluate CNV. e.g. a new sub- or intraretinal hemorrhage, or decreased VA without visible edema with an OCT exam.

If FA is deemed necessary then it must performed no later than 7 days after the exam where visual acuity is measured, that is if it is not possible to obtain a FA on the same day.

Fundus and FA images from the 1 and 2 year follow-up visits are to be sent masked and marked with the patient ID-number to Karina Berg, MD; Dept. of Ophthalmology; Oslo University Hospital HF, Ulleval; 0407 Oslo.

At each exam: the examining ophthalmologist updates the patient history. Intraocular pressure is measured and then an examination of both eyes in mydriasis is performed.

At each exam: the patient receives an intravitreal injection with either Avastin or Lucentis in accordance with the results of the randomization.

New blood tests are to be taken after 2 years in accordance to a provided checklist. These tests are to be taken after the final injection.

Blood test results are to be sent masked and marked with the patient ID-number to Karina Berg, MD; Dept. of Ophthalmology; Oslo University Hospital HF, Ulleval; 0407 Oslo.

Follow-up visits must be carefully planned with the patient in order to be certain that the prescribed follow-up interval is maintained. The patient should receive an appointment for the next visit before leaving the clinic.

If a patient cannot come to a planned follow-up appointment, then she/he is to be contacted by either the study-nurse or the ophthalmologist with the possibility of a serious adverse event (SAE) in mind. A new appointment should then be scheduled.

When to treat again:

The follow-up and treatment interval shall be reduced when there are signs of active CNV. The shortest interval used shall be 4 weeks. The interval shall be extended when there is dry, inactive CNV. The longest interval used shall be 12 weeks.

Signs of active CNV:

Subretinal or intraretinal fluid. Unchanged, increased or new subretinal or intraretinal hemorrhages. Increased size, or leakage as determined by fluorescein angiography. If there is a pigment epithelial detachment (PED) at the time of the baseline examination, then monthly treatments are to continue as long as there is a positive response to the injections. After that point, then extension of the interval can commence. Thus the PED need not be entirely plane before the interval can be extended. If however, the size of the PED lesion should increase, that would denote a recurrence, thus requiring an interval reduction.

If a patient comes for an extra, unplanned visit because of symptoms suggesting a recurrence of CNV, then they may be treated if there are signs of active CNV as long as it has been at least 4 weeks since the last injection. If the patient is treated, then the new follow-up and treatment interval is to be two week less than the time to this recurrence. The shortest interval is however 4 weeks.

When to withhold treatment:

Non-responder:

If there is no response to treatment after 3 injections given with a 4-week interval, as determined by:

increased edema as measured by OCT regardless of visual acuity, or unchanged edema and no improvement of visual acuity (<5 letters on the ETDRS chart from baseline), then the patient shall be removed from the study in order to be offered alternative treatment (e.g. combined treatment with PDT). Note that any reduction of edema is considered response, regardless of visual acuity.

In the event of an AE/SAE related to the intravitreal injection, further treatment is postponed until the condition is cured alleviated. Examples of such events are:

Moderate intraocular inflammation defined as ≥2+ in the anterior chamber or 2+ vitritis (16-25 cells per mm² in the anterior chamber or vitritis giving impaired but not fully obstructed visualization of the optic disc and retinal blood vessels).

Intraocular pressure (IOP) ≥30 mm Hg as measured before an injection. Continued intravitreal treatment is permitted when the IOP is 30 mm Hg with or without IOP reducing medication.

Vitreous hemorrhage with loss of ≥30 letters on the EDTRS chart. Continued intravitreal treatment is permitted when the visual loss has improved to <30 letters.

New retinal tear, break or detachment (including macular hole). Continued intravitreal treatment is permissible one week after appropriate treatment of a retinal break.

Localized infection/inflammation, e.g. conjunctivitis, keratitis, episcleritis/scleritis or endophthalmitis.

Pharmaceutical management:

The study nurse is responsible for ordering Avastin and Lucentis, and is to assure that the vials are stored correctly in the below prescribed manner.

Avastin and Lucentis must be stored refrigerated at a temperature of 2-4 degrees Celcius.

The drugs are to be stored in the original packaging and must not be used after the marked validity date. The vials should be stored in a dark environment.

Blinding/masking procedure:

Whether the patient is receiving Lucentis or Avastin is masked from the physician, patient and other personnel, but not from the nurses who prepare the injections.

Medicine is retrieved from local storage to the injection room. A vial is used for only one patient. (Avastin 4 ml/vial or Lucentis 0.23 ml/vial.) The batch number of the vial is registered by the study nurse. The vial's rubber membrane is to be disinfected with alcohol which must evaporate prior to filling the syringe.

The study nurse and assisting nurse are to be behind a screen when filling, under aseptic conditions, the syringe with the drug the patient has been randomized to receive. The nurse shall personally and without any delay give the syringe to the study ophthalmologist who performs the injection. The study ophthalmologist is to be blind with regards to the contents of the syringe.

The study nurse performing these duties must not divulge the contents of the syringe to the patient or any other person at the department.

Injection procedure:

Aseptic technique is to be used by the nurse and doctor when preparing and giving the injections.

Topical anesthetic eye drops are given 3 times, or according to local customary procedure, in the study eye.

The skin around the eye, the eyelids and eyelashes of the study eye ar to be cleansed with 5 percent povidone iodine.

5 percent povidone iodine is given in the upper and lower fornices in the study eye. The patient should then keep their eyes closed for a minimum of 90 seconds.

A sterilized eyelid speculum is used to open the eyelids securely. The conjunctiva and eye are to be irrigated with sterile aqueous NaCl solution. A sterilized caliper is used to mark the injection site 3.5-4.0 mm posterior to the limbus.

0.05 ml of the pharmaceutical is given as an intravitreal injection. A single dose of chloramphenicol eye ointment is given after the injection.

Possible complications after intravitreal injection:

The probability of serious complications after intravitreal injection is very small. Complications such as endophthalmitis, vitreous hemorrhage or retinal detachment each have a known incidence of 0.1 percent. Corneal erosion occurs occasionally after an injection. Treatment for this is chloramphenicol ointment.

Adverse Events (AE):

Adverse events are the occurrence of, or worsening, of symptoms, disease, or the perception of such, regardless of the causality. AE can thus consist of medical conditions not previously observed in the patient, but also may consist of preexisting medical conditions that worsen or change in character during the study period. Any AE from the time of recruitment to the end of the study period shall be reported. The Case Report Form (CRF) for AE is to be filled in and sent to Ulleval University Hospital.

Patients who have left the study, irrespective of the reason, are to be contacted either by the study nurse or the study doctor 30 days after the last examination. This is to ascertain whether an AE has occurred.

Serious Adverse Events (SAE):

SAE are defined below. If an SAE occurs then follow-up shall be rigorous so that it will be possible to report significant changes in the patient's condition. An SAE can possibly lead to the exclusion of the patient from the study. In the event of an SAE, a report must be filed per telephone within 24 hours to Karina Berg, MD; Dept. of Ophthalmology; Oslo University Hospital. The CRF for SAE is to be filled in and sent to Ulleval University Hospital.

Criteria for SAE:

Fatality Life threatening disease/condition Events that lead to, or extend, hospital admission. This does not include planned hospital admission for diagnosis or elective surgery of an early known condition.

Events that result in permanent or significant functional loss. Birth anomalies or defects in neonates who have been exposed to the drugs used in the study.

Events that are judged to be medically significant by the study doctor; e.g. events that are not imminently life threatening but are highly significant and perhaps demand intervention in order to avoid serious consequences.

Criteria for ocular SAE:

Events that demand surgical intervention in order to avoid permanent loss of vision.

Severe intraocular inflammation defined as 4+ in the anterior chamber (50 cells per square mm possibly with fibrin in the anterior chamber) or 4+ vitritis (no visualization of the fundus).

Loss of vision to ≤ light perception in the study eye. Loss of visual acuity ≥30 letters in the study eye since the previous examination.

Reporting of AE and SAE shall include:

The type of event. The grade of the event (mild, moderate, severe). The time of the event. The result of the event Is the event a result of the study drug (likely or unlikely)? Information as to whether the event has resulted in a change in study treatment.

Ethics:

The cost of treating patients with Lucentis has, by physicians and others in health care, been judged to be unreasonably high. It has been questioned whether it is justifiable to allocate such a large proportion of health care resources to this treatment (8). Many patients have AMD only in one eye, and therefore have partially retained their vision. Because of the high cost of treatment, there are some national health care systems which fund treatment of one eye only when both eyes are afflicted. To date published data as well as practical experience of treating patients with Avastin leads us to believe that its efficacy is equivalent to Lucentis. From a public health resource perspective, there are enormous gains to be made by choosing Avastin for treatment of AMD. It is also theoretically possible that Avastin use may be advantageous compared to Lucentis, as it's longer half life may facilitate a longer treatment interval. If, on the other hand, Lucentis is determined to be more effective than Avastin, i.e. has a higher rate of response, it still might be so that the difference isn't great enough to motivate the higher cost of treatment. Although Lucentis is approved by the authorities in many countries, it is not a given that it is superior to Avastin. Patients participating in this study will thus be informed that two treatments are being compared, where it is probable that the two are equally efficacious, and that is important to prove this considering the great difference in cost. We will also point out that there is considerable international experience of intravitreal treatment with Avastin, and that the experience thus far has been good and side effects are uncommon.

Statistics:

When comparing mean change in VA (visual acuity) from baseline with VA after two years of treatment (DELTA_VA) in the two groups, a two-sided independent sample t-test will be used, with a 5 percent significance level. We want our study to have at least a 90 percent test power in order to detect a statistically significant difference in DELTA_VA between the treatment groups, provided that the true mean DELTA_VA difference is at least 5 letters. Based on previous research we assume that the standard deviation of DELTA_VA will be 15 letters in each group. It may then be shown that at least 380 patients must complete our study. As we expect a drop-out rate of about 10 percent, we have decided to include 420 patients in the study.

This sample size calculation has been performed in cooperation with Leiv Sandvik, Professor in Biostatistics at the University of Oslo.

References

1. Rosenfeld PJ, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006; 355:1419-31.

2. Rich RM, Rosenfeld PJ et al. Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Retina 2006, 26; 495-511.

3. Spaide RF et al. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina 2006; 26: 383-390

4. Rosenfeld PJ. Intravitreal Avastin : the low cost alternative to Lucentis? Am J Ophthalmol 2006; 142:141-3.

5. Spaide R, Ranibizumab According to Need: A Treatment for Age-related Macular Degeneration. Am J Ophthalmol. 2007; 143(4): 566-83.

6. Yannuzzi LA, Neovascular AMD: out of the forest and into the trees. Retina 2007; 27(6):655-61.

7. Vaughn Emerson M, et al. Intravitreal bevacizumab (Avastin) treatment of neovascular age-related macular degeneration. Retina 2007; 27:439-44.

8. Wong K, Kyle G. Some ethical considerations for the "off-label" use of drugs such as Avastin. Br J Ophthalmology 2006; 90:1218-19.

9. Dafer RM, Schneck M. Intravitreal ranibizumab and bevacizumab; a review of risk. Semin Ophthalmol. 2007; 22(3):201-4.

10. Ziemssen et al. Tuebingen Bevacizumab Study Group: Safety monitoring in bevacizumab (Avastin) treatment: retinal function assessed by psychophysical (visual field, colour vision) and electrophysiological (ERG/EOG) tests in two subgroups of patients. Int Ophthalmol 2008; 28:101-109.

11. Cugati S, Cumming RG, Smith W, Burlutsky G, Mitchell P, Wang JJ. Visual impairment, age-related macular degeneration, cataract and long-term mortality: the Blue Mountains Eye Study. Arch Ophthalmol 2007; 125(7):917-24.

12. Scappaticc FA, Skillings JR, Holden SN et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 2007; 99:1232-1239.

13. Fung AE, Rosenfeld PJ et al. The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 2006; 90: 1344-1349.

14. Wu L, Martinez-Castellanos MA et al. Twelve months safety of intravitreal injections of bevacizumab (Avastin): results for the Pan-American collaborative retina study group (PACORES). Graefes Arch Clin Exp Ophthalmol. 2007; 246: 81-87.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Conditions

Wet Age-Related Macular Degeneration

Intervention

Bevacizumab (Avastin), Ranibizumab (Lucentis)

Location

Department of Ophthalmology, Oslo University Hospital
Oslo
Norway
0407

Status

Recruiting

Source

Ullevaal University Hospital

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:13:33-0400

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A recombinant humanized monoclonal antibody fragment that binds VEGF-A to prevent its binding to VEGFR-1 and VEGFR-2 receptors. This activity reduces vessel permeability and angiogenesis in the treatment of neovascular age-related MACULAR DEGENERATION.

A form of MACULAR DEGENERATION also known as dry macular degeneration marked by occurrence of a well-defined progressive lesion or atrophy in the central part of the RETINA called the MACULA LUTEA. It is distinguishable from WET MACULAR DEGENERATION in that the latter involves neovascular exudates.

Specialized ophthalmic technique used in the surgical repair and or treatment of disorders that include retinal tears or detachment; MACULAR HOLES; hereditary retinal disease; AIDS-related retinal infections; ocular tumors; MACULAR DEGENERATION; DIABETIC RETINOPATHY; and UVEITIS.

A retrogressive pathological change in the retina, focal or generalized, caused by genetic defects, inflammation, trauma, vascular disease, or aging. Degeneration affecting predominantly the macula lutea of the retina is MACULAR DEGENERATION. (Newell, Ophthalmology: Principles and Concepts, 7th ed, p304)

A form of RETINAL DEGENERATION in which abnormal CHOROIDAL NEOVASCULARIZATION occurs under the RETINA and MACULA LUTEA, causing bleeding and leaking of fluid. This leads to bulging and or lifting of the macula and the distortion or destruction of central vision.

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Ophthalmology
Ophthalmology is the branch of medicine that is devoted to the study and treatment of eye diseases. As well as mild visual defects correctable by lenses, ophthalmology is concerned with glaucoma, uveitis and other serious conditions affecting the eye, ...


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