Influence of Prostaglandins on Ocular Blood Flow in Glaucoma Patients
Condition: Open-Angle Glaucoma
MeSH terms: Glaucoma; Glaucoma, Open-Angle
Study type: Interventional
Phase: Phase 4

Summary: 
      Vasoactivity of topical drugs may be of prognostic relevance in glaucoma. There is very
      little information for a major class, the prostaglandin analogues with regard to this aspect.
      The purpose of this study is to compare the effect of travoprost 0.004% and latanoprost
      0.005% on choroidal blood flow and retinal vascular diameter in glaucoma patients. After
      washout of current topical medication, intraocular pressure (IOP) in both eyes (Goldmann
      applanation tonometry), choroidal blood flow (laser Doppler flowmetry) and retinal vessel
      diameter (Retinal Vessel Analyzer) in one randomly selected eye will be measured at baseline,
      after two weeks and after 4 weeks of treatment with travoprost or latanoprost QD, in a
      randomized, double masked 2-way cross-over study in 20 open angle glaucoma patients.
    

Detailed description: 
      Background Glaucoma is a leading cause of blindness worldwide. Chronic primary open-angle
      glaucoma is the most common form among Caucasian patients. The key feature of glaucoma is
      damage to the optic nerve head, which is not necessarily related to an increase in
      intraocular pressure (IOP). The actual therapeutic armamentarium for glaucoma includes
      miotics, beta-blockers, alpha-adrenergic agonists, oral and topical carbonic anhydrase
      inhibitors, and prostaglandin analogues, the latter being the latest addition to the
      armamentarium and the most potent topical IOP lowering drugs. Besides IOP, ocular blood flow
      alterations have been incriminated in glaucoma. Hence, it is of relevance to assess the
      effect of anti-glaucomatous drugs on ocular blood flow.

      Rationale of the study Vasoactivity of topical drugs may be of prognostic relevance in
      glaucoma. There is very little information for a major class, the prostaglandin analogues
      with regard to this aspect. The vascular activity of two prostaglandin analogues, travoprost
      0.004% and latanoprost 0.005%, which are already on the Swiss market, will be tested.

      Study objectives Primary Objective: To assess the effect of two prostaglandin analogues,
      travoprost 0.004% and latanoprost 0.005% on choroidal blood flow in primary open-angle
      glaucoma patients.

      Secondary Objective: To assess the effect of travoprost 0.004% and latanoprost 0.005% on
      retinal vascular diameter in primary open-angle glaucoma patients.

      Investigational plan Primary open-angle-glaucoma patients will be assessed regarding
      inclusion/exclusion criteria. After a washout of current topical medication (beta-blockers
      and prostaglandin analogues: 4 weeks; topical carbonic anhydrase inhibitors and
      alpha-agonists: 2 weeks; Pilocarpine: 1 week), half of the patients (17 patients) will be
      treated with travoprost 0.004% for 1 month while the other 17 patients will be treated with
      latanoprost 0.005% for the same duration. Efficacy and safety variables will be assessed at
      baseline, after 2 weeks, and after 1 month of treatment. After this first period, the
      patients will be washed out for 4 weeks and baseline efficacy and safety parameters will be
      obtained. Afterwards, the patients will be treated with the other compound. Again, efficacy
      and safety variables will be assessed after 2 weeks and after 1 month of treatment.

      Design Single center, randomized, double masked 2-way cross-over design. Randomization The
      patients will be divided in two groups, and each group will alternatively be started with
      either travoprost 0.004% or latanoprost 0.005%. Recruitment and management will be carried
      out by a study nurse masked to baseline blood flow measurement results. Masking and
      randomization procedures will be entrusted to Alcon PHARMACEUTICAL AG. The drug products for
      this study will be prepared by the following procedure: Each product will be labeled during
      independent labeling operations. For this study four different products will have to be
      labeled: travatan medicin A, travatan medicin B, xalatan medicin A and xalatan medicin B.
      Each labeling operation will start and end with a line clearance procedure and each labeling
      order will be 100% inspected by a person that is independent from the person who will do the
      labeling. On each label the patient number will indicated. The labeling order will be
      initiated by using the randomization list that indicates which product has to be labeled for
      which patient. The randomization sequence will be pulled from a uniform distribution with an
      arbitrary seed (Randomization Performed with SAS 8.2 on NT using RANUNI [seed]). During each
      independent labeling operation also the disclosure labels will be provided with the same
      patient number than indicated on the open label. After release of each independent labeling
      procedure, the assembly of the packaging of two carton boxes in an assembly carton box will
      start for each patient. The assembly box will also be also labeled with patient
      number/investigator number and protocol number. Release of the labeled samples will always be
      done by an independent QA department.
    

Intervention name(s): travoprost 0.004% (drug); latanoprost 0.005% (drug)
Intervention type(s): Drug; Drug
Intervention description(s): local drop application; local drop application
Intervention MeSH terms: Travoprost; Latanoprost
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Glaucoma; Blood flow; Choroid; Retina; Prostaglandin analogues