Healing of NSAID-Associated Gastric Ulcers in Patients Continuing NSAIDs

Results

Patients and Disposition

The study was conducted from February 2001 to April 2003. In all, 440 patients were randomized at 75 study sites as follows: Bulgaria, 89 patients from nine sites; Indonesia, 51 patients from two sites; Romania, 45 patients from seven sites; the Ukraine, eight patients from three sites, and the US, 247 from 54 sites. Patient disposition in the study is shown in Figure 1. Of the 440 patients randomized, 30 were not included in the primary efficacy analysis because of no study drug use, the lack of a documented baseline GU, or a GCP violation at a single site identified after the site was audited. Of 410 patients included in the primary efficacy analyses, 88 (21%) were in Bulgaria, 51 (12%) were in Indonesia, 45 (11%) were in Romania, 8 (2%) were in the Ukraine and 218 (53%) were in the United States.

Figure 1.  (click image to zoom)

Patient disposition. GCP, good clinical practice; NSAID, non-steroidal anti-inflammatory drug; GU, gastric ulcer. * Some patients had more than one type of protocol deviation.      

Baseline demographics and characteristics for patients included in the efficacy analysis are summarized in Table 1 . The study population included more women than men, and most patients were white. The proportion of patients with positive H. pylori status, as determined by histology, was similar among the three groups and included 13.8% (30 of 218) of patients in the United States and 40.1% (77 of 192) of patients in the non-US countries. The most common chronic condition for which patients were taking NSAIDs was osteoarthritis (51% of the patients). Across the three treatment groups, most patients (88%) used non-selective NSAIDs; the most commonly used non-selective NSAIDs were aspirin, diclofenac, ibuprofen, and naproxen. Of these patients, approximately 14% (51/362) used only low-dose aspirin (80 to 325 mg per day). Baseline OGD findings showed that the mean maximum GU size was approximately 8.2 mm, and 129 patients (31%) had GUs > /=10 mm ( Table 2 ). Also, four patients (< 1%) had baseline GUs of maximum size < 5 mm. The GU healing results for these four patients were included in the mITT analysis for completeness. Excluding the healing results for these patients would not have changed the results of the analysis. Only 34 patients included in the efficacy population had concurrent baseline DUs ( Table 2 ).

Overall, for patients in the efficacy analysis, compliance with study medication was 97% (396 of 410 patients) and was similar among the three treatment groups. NSAID compliance was also generally similar among the treatment groups with an overall compliance rate of 88% (361 of 410) of the patients.Efficacy

Table 3 reports the GU healing rates at 4 and 8 weeks. Although the observed GU healing rates at week 8 were numerically higher with the esomeprazole treatments than with ranitidine, these results were not statistically significant. In contrast, at week 4, the observed GU healing rates were significantly higher for patients treated with esomeprazole 40 and 20 mg than for patients treated with ranitidine ( Table 3 ). The observed GU healing rates in the esomeprazole groups compared with the ranitidine group are shown for subgroups evaluated according to age group (Figure 2), baseline H. pylori status determined by histology (Figure 3), and non-selective vs. selective baseline NSAID used (Figure 4).

Figure 2.  (click image to zoom)

Gastric ulcer (GU) healing rates by age. E40, esomeprazole 40 mg once daily; E20, esomeprazole 20 mg once daily; R150, ranitidine 150 mg twice daily (mITT population).      

Figure 3.  (click image to zoom)

Gastric ulcer (GU) healing rates by baseline Helicobacter pylori status determined by histology. E40, esomeprazole 40 mg once daily; E20, esomeprazole 20 mg once daily; R150, ranitidine 150 mg twice daily. †Baseline H. pylori status was missing for one patient in the esomeprazole 40-mg group (mITT population).      

Figure 4.  (click image to zoom)

Gastric ulcer (GU) healing rates by baseline non-steroidal anti-inflammatory drug (NSAID) type. The non-selective NSAID group includes patients who were taking a cyclooxygenase (COX) 2-selective NSAID if they were also taking a non-selective NSAID (including low-dose aspirin). E40, esomeprazole 40 mg once daily; E20, esomeprazole 20 mg once daily; R150, ranitidine 150 mg twice daily. †One patient in the ranitidine 150-mg group was not taking an NSAID before or during the study (mITT population).      

The observed GU healing rates were reanalysed including the 15 patients (five in each treatment group) that were excluded from the mITT population because of GCP violations. The results of this reanalysis provided healing rates that were almost identical to those seen in Table 3 . Therefore, removing these patients from the mITT analysis did not affect the findings of this study.

As a secondary analysis of GU healing, the estimated GU healing rates through the final visit (based on Kaplan-Meier estimation) were 92.1% (95% CI, 87.4%-96.8%), 94.6% (95% CI, 90.7%-98.5%) and 89.2% (95% CI, 83.7%-94.7%) in the esomeprazole 40-mg, esomeprazole 20-mg and ranitidine groups, respectively. Estimated GU healing rates through week 4 (based on Kaplan-Meier estimation) were 71.6% (95% CI, 63.9%-79.4%), 75.2% (95%CI, 67.8%-82.5%), and 58.4% (95% CI, 49.9%-66.8%) for the esomeprazole 40-mg, esomeprazole 20-mg, and ranitidine groups, respectively. Comparisons of the time-to-event curves showed that the time to first healing of GUs was significantly different for esomeprazole 40 mg and esomeprazole 20 mg compared with ranitidine, (P = 0.047 and P = 0.002, respectively).

For the 34 patients in the efficacy analysis who had concurrent DUs at baseline, the DU healing rates at week 8 were 90% (nine of 10 patients) with esomeprazole 40 mg, 68.8% (11 of 16 patients) with esomeprazole 20 mg, and 87.5% (seven of eight patients) with ranitidine.Safety

The safety population included 432 patients: 140 patients in the esomeprazole 40-mg group, 145 patients in the esomeprazole 20-mg group, and 147 patients in the ranitidine 150-mg group. The overall percentage of patients with AEs in this study was 56% (79/140) with esomeprazole 40 mg, 58% (84/145) with esomeprazole 20 mg and 58% (85/147) with ranitidine 150 mg. The number of patients with AEs considered by the site investigator to be related to study drug was also similar among the three treatment groups: 12 (9%) for esomeprazole 40 mg, 13 (9%) for esomeprazole 20 mg and 10 (7%) for ranitidine 150 mg. The most commonly reported AEs for esomeprazole 40 mg, esomeprazole 20 mg and ranitidine 150 mg were gastrointestinal and included gastritis [22 (16%), 25 (17%) and 25 (17%) patients, respectively], flatulence [18 (13%), 27 (19%) and 20 (14%), patients respectively], new onset or worsening of existing dyspepsia [14 (10%), 19 (13%) and 18 (12%) patients, respectively], and new onset or worsening of existing nausea [17 (12%), 11 (8%) and 17 (12%) patients, respectively].

Fourteen of the 440 randomized patients had 16 serious AEs (four patients in the esomeprazole 40-mg group, six in the esomeprazole 20-mg group and four in the ranitidine group), but none was the same and none was considered related to treatment. There was one death that occurred due to an unknown cause on the third day of treatment with esomeprazole 20 mg; the investigator did not consider the death to be related to study medication. Of 440 patients, 17 (3.9%) discontinued the study due to AEs; the number in each treatment group was similar. There were no clinically relevant trends in the results of laboratory tests, physical examinations or vital signs.  Printer- Friendly Email This

Aliment Pharmacol Ther.  2007;26(8):1101-1111.  ©2007 Blackwell Publishing
This is a part of article Healing of NSAID-Associated Gastric Ulcers in Patients Continuing NSAIDs Taken from “Nexium Generic Esomeprazole” Information Blog

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Could Your Cat have Fatty Liver Disease?

You may never have heard of Feline Fatty Liver Disease -- but if you don't heed the tell-tale signs, it could cost you your cat's life!

What's Feline Fatty Liver Disease?

If your cat ever loses her appetite or stops eating altogether, you better take her to a vet fast! When a cat stops eating for an extended period of time – say, about 2 weeks – she may die from a condition called fatty liver disease. That’s when fat accumulates within the liver cells.

The medical term for this condition is feline hepatic lipidosis.

Signs of Fatty Liver Disease

You should suspect hepatic lipidosis if your cat refuses to eat, loses weight, acts lethargic, and vomits. You might also notice that the whites of the eyes look yellow from bile pigments.

Bile is a yellowish green digestive fluid secreted by the liver. If the liver isn’t functioning well, the bile won’t get broken down properly.


Causes of Fatty Liver Disease

In humans, fatty liver disease can be caused by excessive drinking. Needless to say, this is never the case with cats. (Don’t ever give your cat any alcoholic drink – you could kill her!)

Vets don’t really know what causes this condition, but cats that fail to eat for an extended period of time, for whatever reason, are at the highest risk.

Cats can stop eating for a lot of different reasons. She might be ill or too stressed out to eat. So it’s a good idea to pay attention whenever your cat loses her interest in food. You’ve got to make sure that the cat is eating.

I didn’t, and I’ve lived to regret it. When my late cat Saki stopped eating, I was so wrapped up in my work that I barely noticed. When I finally noticed, I wasn’t overly concerned.

Saki was a tad overweight (ah, but she had green eyes to die for!), and fat-phobic that I am, I figured she could stand to lose a little weight.

Little did I know that in cats, unlike humans, losing weight from partial – or even worse, total – fasting is dangerous even if it’s only for a relatively short period of time. Apparently, cats metabolize fats and proteins differently than humans.

When a human or cat stops eating, the body starts using its own fat cells for fuel. As you know, for humans, this is the whole point of dieting.

With cats, however, the liver isn’t terribly efficient at processing fat. Most of the fat is stored in the liver cells, and so eventually the liver fails and the cat dies. Not good.

So when Mittens wouldn't eat, I really feared for her life. Until I took over the care of Mittens, my friend's cat, I had never even heard about hepatic lipidosis.

Mittens had been wheezing for some six months. At the time, the vets had no idea what was wrong. They suspected nasal cancer.

When I took Mittens home with me, she was so scrawny she looked like a concentration camp inmate. The resemblance was even more striking because one of her forelegs had been shaved – that’s where the vet had inserted a catheter when they were testing her.

Coaxing Your Cat to Eat

In addition to getting prescription appetite stimulants for her, I tried everything in the books to coax her to eat:

Warmed up canned food (Since I don’t have a microwave, I heated up the can in hot water. Alternatively, I added some hot water to the food and stirred it into a form of gruel.)

Got some of the stinkiest, smelliest food on the market (Mittens was most likely not eating because she couldn’t smell anything.)

Tried dried bonito (tuna) flakes (Many cats love them. Saki used to go ga-ga over them. But it turns out that Mittens is rather indifferent to fish.)

Minced sardines (See above.)

Canned tuna (See above. Caution: Tuna isn’t generally recommended for cats, but when a cat isn’t eating, the most important thing is to get her to eat something, anything.)

Offered canned pumpkin (It’s loaded with vitamins and fiber. Most cats love the taste.)

Human baby food (Plain chicken, turkey, beef. Made sure it didn’t contain onions – they are poisonous to cats.)

Here are a few other things to try to resurrect your cat’s interest in food:

Watered-down chicken broth (with no sodium added)

Clam juice (Add it to the cat’s regular food as flavor enhancer.)

Tuna Dash (Dried powdered tuna)


To entice Mittens to eat, I’d put the food right under her nose – but I don’t think that she was able to smell it even then. I also smeared some food right on her nose and on her lips – sometimes on her paws – so that she would have to lick them. I spoon-fed her too, and she would eat a little then. But it wasn’t nearly enough to sustain her.

The strange thing was that Mittens acted as if she were hungry. She’d smack her lips, and go over to her food bowl – even stick her face in the bowl – and yet she wouldn’t eat.

Escaping the Jaws of Death

I consulted the vet. By this time the results of Mittens’ biopsy were in. She had fungal infection, not cancer!

The vet immediately took her off prednisone, which she suspected was giving Mittens ulcers. In addition to medication to treat her fungal infection, she was also given medicine to treat the ulcers.

In less than a week, Mittens was eating again! We didn’t have to resort to force feeding her or putting tubes in her stomach – that’s something we would’ve had to do as a last resort.

“Great job. I am so very pleased,” the vet beamed at her last check-up. “She’s twice the cat she was before.”

Indeed, we now have a pair of Mittens. Some cat she is.

And what about you? Have you ever brought a cat back from the brink of death? Or coaxed a reluctant cat to eat? Please share any stories you might have.

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The Trials and Tribulations of Giving Your Cat Medicine

If you own a cat long enough, you’ll be faced with the task of medicating the cat. It’s not an easy matter, as many cat owners will attest.

I learned the best way to medicate cats when I had to care for Pixie’s cat, Mittens.

For a while there, what’s wrong with Mittens? became the rallying cry.

It seemed quite likely that she had cancer, lymphoma is probably the most likely one, the vet said.

If so, we can only give her palliative care. She would need radiation and chemotherapy, but that runs into thousands of dollars, and Pixie is in no situation to be able to pay that sort of medical bill. Then the best we could do her is give her prednisone.

Therefore, it was decided that she’d receive prednisone in tablet form.

I’d agreed to take care of Mittens so the job of medicating her fell on me.

After Mittens took prednisone for several weeks, she stopped eating altogether. The vet suspected ulcers so we had her on ulcer medication in addition to appetite stimulants. For a while there I was medicating Mittens 5 times a day!

The vet’s assistant gave me an impromptu lesson in how to wrap a cat tightly with a towel. This renders the cat immobile. Then, using your fingers like pincers you press the cat’s jaws open. That’s the theory, at least. In practice, it never worked for me.


We had to switch Mittens from prednisone in tab form to liquid because I was having the worst problem medicating her. For a cat so scrawny and scraggly, she was amazingly strong and frighteningly ferocious when she resisted. She was also extremely slippery -- her escape acts rivaled those of Houdini. Fortunately, I was unscathed but Pixie received a huge gash in her hand when pilling Mittens. My friend John, who is not allergic to cats, somehow ended up with an allergy-like respiratory attack that ended in a doctor's visit. His medical records to date list that he came in due to a respiratory distress from "wrestling a cat."

The vet agreed that some cats are almost impossible to pill. Like one of her cats. Even though she and her husband are both vets, they have to work in tandem to get the pill down the cat's throat -- and even then, they barely succeed.

John bought a syringe-like pill popper used for medicating cats and dogs, but I didn't have to resort to that after all once we switched to liquid medication. As to the ulcer meds, I just ground them up and drew the powder into the syringe when I gave Mittens her liquid prednisone.

Pixie discovered a somewhat pricey, freeze-dried chicken treats that Mittens loved from a posh pet store in an upscale neighborhood. (This cat is definitely costing megabucks.) The idea was that I would give Mittens this treat as soon as I medicated her. It worked. Since then, Mittens has been quite subdued, almost cooperative. Now, when I pull up the towel, she merely cringes a bit – maybe emits a resigned meow – and flattens herself. But she lets me wrap the towel around her neck like a bib and remain still while I insert the syringe into her mouth.

Easy breezy.

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