1. The Aleve (Naproxen) we are studying along with many NSAID's are widely used already by many patients. Many patients are self mediating themselves without a PPI to make it safer. ˙ So pts are already self medicating with them without getting scoped. Therefore, the population being studied is healthier than someone referred to a GI Doc because they are not feeling well.
2. If I were the endoscopist, I would not biopsy anybody for the purpose of this study.˙ This is not what this trial is about. It's about trying to get a combo pill Naproxen-Nexium on the market so that fewer patients suffer NSAID associated ulcers.
3. The pt will be told up front by me regarding this biopsy deal.
4. The endoscopist should be instructed to do the following:
a. If something looks bad enough that you think it requires a biopsy, (especially if it is on the first endoscopy), then let's drop the pt out of the study and ask them to see their own GI Doc & get a repeat upper endo/Bx.
b. If it looks like a Bx would be nice but not 100% necessary (that is, you recognize the pt will have 4 endo's during the trial & you'll have the unusual opportunity to utilize serial upper endo's to follow this pt), then just perform the upper endo.
5. The study doesn't reimburse us if pt flunks out because of an abnormality that is exclusionary. For example, if there's a cancer in the stomach on the first endoscopy or if there is any reason to Bx.
6. We can indemnify the endoscopist.˙ That is, tell them this pt would be (if they were not participating in our Drug Study) on either Naproxen or Naproxen/Nexium without talking about endoscopy were they not in a trial.˙ So, for the purpose of the study, we are already doing a good thing by screening them with an upper endo.˙ And, we are going to do 4 serial upper endo's to follow safety over time.˙ This level of checking is not seen outside of a clinical trial. That is, to qualify for the study you have to already be on an NSAID. The study is going to educate pts about the risk of NSAID induced ulcer and give half of them Nexium. Everyone will obtain 4 serial upper endo's to make it safer and hopefully prove adding the Nexium cuts down on NSAID related PUD
a. That is, a pt on Naproxen usually does not require a screening upper endo, much less 4 serial upper endo's.
b. The Naproxen/Nexium arm should have even less chance of˙having any pathology on upper endo.
c. If something abnormal is present on the last (4th) upper endo, we could consider Bx then.˙ After all, the Bx is usually done thinking this will be the last time this pt will have a scope in their stomach.˙
d. At the end of the trial, the sponsor will look more favorably at paying for a Bx than asking to do it earlier on.˙ They will want to thank the pt and make sure their study is not associated with cancer.
7. Keep in mind, if a pt required an upper endo, they would not qualify for this study to begin with. Our population is extremely low risk pts who could be using the study drug anyway without any GI tract protection.
Sincerely:
Joseph Saponaro, MD, DABIM, FACP, CPI, CCI, CCTI, CCRC, CCRP
PI (Principal Investigator), DSI (Drug Study Institute)
Board Certified Internist, JPMC (Jupiter Preventive Medicine Center)
DABIM (Diplomat American Board of Internal Medicine)
FACP (Fellow American College of Physicians)
CPI (Certified Physician Investigator) by the AAPP (American Academy of Pharmaceutical Physicians)
CCTI (Certified Clinical Trial Investigator) by the ACRP (Association of Clinical Research Professionals)
CCI (Certified Clinical Investigator) by the DIA (Drug Information Association)
CCRC (Certified Clinical Research Coordinator) by the ACRP (Association of Clinical Research Professionals)
Member, the American College of Forensic Examiners Institute of Forensic Science
CCRP (Certified Clinical Research Professional) by SoCRA (Society of Clinical Research Associates)
Member, SIMPD (Society for Innovative Medical Practice Design)
Member, ACPM (American College Preventive Medicine)
Ethics Committee Member, Jupiter Medical Center
IRB Member, Jupiter Medical Center
Founder, CertifiedResearchers.com
NSAIDs
NSAIDs or Non-Steroidal Anti-Inflammatory Drugs are a group of drugs commonly used to treat arthritis because of their analgesic (pain-killing), anti-inflammatory, and antipyretic (fever-reducing) properties.
The mechanism of action of NSAIDs is the inhibition of the enzyme Cyclooxygenase (or COX, for short), which catalyzes arachidonic acid to prostaglandins and leukotrienes. Arachidonic acid is released from membrane phospholipids as a response to inflammatory stimuli. Prostaglandins establish the inflammatory response.
There are two forms (isoforms) of COX: COX-1 and COX-2. COX-1 helps maintain good health; ie: provide mucus coat to the stomach lining. When COX-1 is blocked, side effects like stomach ulcers occur. COX-2 is formed in response to an injury or inflammation. When COX-2 is blocked, pain is diminished.
There are many NSAIDs available. High dose Aspirin (two 325 mgm pills 4x daily) acts like an NSAID by blocking one COX-1 for every COX-2. The first generation NSAIDs block two COX-2s for every COX-1 and include: Ibuprofen, Motrin, Advil, Aleve, Naprosyn, Anaprox, Voltaren, Arthrotec, Dolobid, Lodine, Ansaid, Indocin, Orudis, Toradol, Relafen, Daypro, Feldene, Clinoril, Tolectin, Mobic, and others. The second generation (COX-2 inhibitors) block many (about 100) COX-2s for every COX-1, and are theoretically safer for the stomach and include: Celebrex, Vioxx, and Bextra. (Only Celebrex is left on the market).
There has been negative public opinion beginning in September 2004 about NSAIDs in general that begun with Merck withdrawing Vioxx from the market over concerns that there were more Cardiac and Cerebral events than placebo. The APPROVe trial of Vioxx showed 20 per thousand more events than placebo. This was not a trial designed to look at safety, however. It was to prove that Vioxx prevented colon cancer. That is, they didn't stratify its subjects to heart attach or stroke risk. Merck thought since there was a suspicion that it might be implicated in higher risk; they voluntarily pulled it from the market. An earlier trial, VIGOR, alluded to some Vioxx problems also. Subsequently similar concerns have arisen with Celebrex and Naproxen. But they remain on the market and are widely prescribed.
This? is not surprising since all the NSAIDs have the same basic mechanism of action; that is, blocking COX-2 to alleviate pain.