Full HTML 05 V1 I4

Prospective Study on Effectiveness of H.pylori Radication Therapy and Utilization of Acid Suppressant Medications in Patients With Peptic Ulcer Disease


A.SRINIVASAN*, T.VENKATACHALAM, ,G.THOMOTHARAN, KC.ARUL RAKASHAM, FEBA SOSA KURIEN,
Department of Pharmacy practice, JKKMMRF college of Pharmacy.The Tamilnadu Dr MGR Medical university, Erode, TamilNadu, India

ABSTRACT

The study is to assess the Effectiveness of Helicobacter Pylori Eradication Therapy and Utilization of Acid Suppressant Drugs in patients with Peptic ulcer disease at Gastroenterology department of manak hospital at kerala on May 2012 to February 2013. Totally 280 patients profile is taken for the study from this 82 patients age comes below 65 years and 198 patients were above 65 years, Proton pump inhibitors has prescribed to 208 patients by Omeprazole has given to 122 patients followed by Pantoprazole to 87 patients and others PPIs for 71 patients, histamine receptor antagonist has given to 44 patients and other  ASMs used to 34 patients.66% patients prescriptions has changed from  PPIs  to H2RAs and similarly 46% prescription has changed from  H2RAs to PPIs. 74% patients  prescribed ASDs for 1- 3 month duration and remaining 26% patients receiving over prescribing, ASMs has prescribed to 41% patients is for correct indications (justified) the remaining was considered as unjustified cases.

60 patients undergone H.Pylori eradication therapy, 51 out of 60 patients receives complete H. Pylori eradication by using Tetracycline, Bismuth chelate with Metronidazole combination therapy. The current study found that quadruple therapy is highly effective, well –tolerated anti –Helicobacter regimen in primary health care setting.  General practitioners to review their ASMs prescribing pattern to treat the in appropriate indications and prophylaxis uses.

Keywords: PUD- Peptic Ulcer Disease, GERD –Gastro esophageal reflux disease, SUP –stress ulcer disease, Gastroenterology.

INTRODUCTION  

Peptic ulcer disease (PUD) differs from gastritis and erosions in that ulcers typically extend deeper into the muscularis mucosa. There are three common forms of peptic ulcers: Helicobacter pylori –associated, non-steroidal anti-inflammatory drug (NSAID)–induced, and stress ulcers.

The natural course of chronic PUD is characterized by frequent ulcer recurrence. Approximately 60% to 100% of ulcers recur within1 year of initial ulcer healing with conventional antiulcer regimens. The most important factors that influence ulcer recurrence are Helicobacter pylori infection and NSAID use. Other factors include gastric acid hyper secretion, cigarette smoking, and alcohol use, a long duration of PUD, ulcer-related complications, and patient noncompliance. The cause of ulcer recurrence is most likely multifactorial. Eradication is defined as the presence of negative tests for H pylori 4 weeks or longer after the end of antimicrobial therapy.

Recommendation for pharmacological therapy

First line therapy should be started with proton pump inhibitors, usually based on three drug regimen for a minimum of 10 days. But 10 to 14 days are preferred. suppose  it is not gone well a second course is preferred  which contain PPI based three drug regimen and different antibiotics or a four drug regimen with bismuth subsalicylate, metronidazole, tetracycline and a proton pump inhibitors should be used.

Treatment with a conventional antiulcer drug (H2RA, PPI, or sucralfate  is an alternative to Helicobacter pylori  eradication, but it  is discouraged due to the high rate of ulcer recurrence and ulcer-related complications associated with these regimens. Concomitant therapy (e.g., H2RAs and sucralfate or an H2RA and a PPI) is not recommended because it adds to drug costs without enhancing efficacy. Maintenance therapy with a PPI or H2RA is recommended for high-risk patients with ulcer complications.

Aim And Objective

  1. To evaluate inappropriate prescribing.
  2. To determine the ratio of step up and step down therapy.
  3. To evaluate the effect of H.Pylori eradication therapy.
  4. To report the efficacy of Quadruple therapy in primary health care for patients with PUD.

MATERIALS AND METHODS

Study Site:-

This observational based prospective study conducted in the Gastroenterology department of manak hospital at May 2012 to February 2013.

Designing Of Data Collection Form:

A suitable data collection form was designed it contain Demograpical details, past medical history, drugs prescribed by generic name, laboratory datas, It includes a question about the patients satisfaction to the cost of acid suppressant drugs they used. Time taken to complete the question is around 4 minutes.

Inclusive Criteria

  • Patients in gastro enterology department who receiving ASMs in their prescription.
  • Patients with peptic ulcer including dyspepsia, gastric, duodenal and stress ulcer are included in the study.
  • Patients with other conditions along with peptic ulcer such as osteoporotic, alcoholic, smokers are enrolled in the study.
  • Age above 15 is included in the study.
  • Both the outpatients and in patients are included.

Exclusive Criteria

  • Patients with other chronic disease such as gastric cancer and MALT are excluded from the study.
  • All ICU and emergency care patients are omitted from the study.
  • Complicated diseases associated with peptic ulcer such as cystic fibrosis, chronic pancreatitis, crohns disease , coronary artery disease , hyperparathyroidism and hepatic cirrhosis are excluded from the study.
  • Patients with bacterial infections other than Helicobacter pylori infection such as Herpes simplex , tuberculosis etc  are omitted from the study.

STUDY PROCEDURE

Data has collected from patients with a history of peptic ulcer documented by endoscopy or serology and who were still taking acid suppressants to control symptoms such as dyspepsia. And also noted the patient prescription containing ASMs for unjustified indication in the GE department. Other important factors noted that the duration time, side effects and category of ASMs used, and also ulcer had been induced by NSAIDs or aspirin has been included. Collected data has compared with ASHP therapeutic guidelines and FDA approved prescribing information.

Patients were divided into two categories according to the endoscopic and serology report that One group having HP-+ve result and others having HP- -ve report. Case histories are then consulted to find out whether they undergone H.Pylori eradication therapy or they still on maintenance ASMs therapy. Data regarding the H.Pylori eradication therapy are consulted to evaluate the effectiveness of therapy. Follow up also noted for 6 months, group having HP+ve result was endoscoped to test for cure or blood samples are collected before and after 6 months follow-up treatment. Success was defined if the test shows H. Pylori negative.

A questionnaire is developed according to COOP functional status. It assess seven 6 domains of functional health; physical fitness, daily activities, social activities ,change in health , pain and overall health. Each domain is covered by a single question to be answered on a yes or no question. Patients were asked to answer the question prior to, and at 6 weeks and 6 months after treatment.

Ethical committee approval for the study was obtained from the institutional ethics committee. Confidentiality and anonymity of the patient`s information were maintained during and after the study. Oral and written informed consent was obtained from participated patients.

All data’s were coded, entered and analyzed using statistical package.(2-WAY ANOVA).Result was expressed in mean, standard deviation, in percentage, 95% confidence interval and p- value was determined.

RESULTS

280 patients are participated in this study.  Result of the study has presented in 2 main parts it includes Utilization of acid suppressant drugs and Effectiveness of H.Pylori eradication therapy.

Gender Wise Distribution

Fig 1 shows in 280 patients received different types of ASMs. Current study shows 22% difference in bases of sex.

Fig 1: prevalence of peptic ulcer according to sex.

Age Wise Distribution

Table1: proportion of drug users according to age.

Age distribution  

(in years)

Number of patients

(N = 280)

Percentage(%)
15 – 44 14 5%
44 – 65 68 24%
>_ 65 198 71%

Table 1 shows 71 %  Patients age comes under  65 years  and above old group, 24% comes under 44- 65 age group and.

Step- Up Therapy and Step down Therapy

Fig 2 Step- up Therapy and Step down Therapy

Fig 2 shows 185 patients prescription changed to Step-down therapy is evaluated by the initial prescribing of  PPIs for peptic ulcer disease may be changed to H2RAs and similarly 95 patients prescription changed to step up is evaluated by the initial prescribing of H2RAs for peptic ulcer disease may be changed to PPIs.

Duration of Asms Therapy

Table 2 indicates the duration of acid suppressant medications prescribed by physicians. The maximum recommended treatment duration for acid suppressant medications is 4 to 8 weeks.

Table 2: Duration Of Asms Prescribed In Patients

Duration of ASMs Therapy No of patients (N) Percentage(%)
1-3 Months 205 73%
3-6 Months 61 22%
6-12 Months 12 4%
More than 1 years 2 1%

 

Table 2 Shows 74%  patients  prescribed ASDs for 1- 3 month, 24% physicians prescribed  acid suppressant drugs for 3-6 month, 4% patients prescribed acid suppressant medication for 6 -12 month and some would prescribe ASMs for more than 1 year in the treatment of acid peptic disorders which is negligible.

Different Types Of Asms Prescribed In Patients.

Fig 3: proportion of acid suppressant drugs used as a first line therapy.

Fig 3 shows various ASMs prescribed to different patients that is Proton pump inhibitors (74%)  > histamine receptor antagonist (16%) >  antacid and prokinetics (10)% > others (2%).

Distribution of Proton Pump Inhibitors Used In Patients                                         

Table 3 shows the proportion of Proton Pump inhibitors in patients with ulcer disease., Omeprazole prescribed to 43% of pantoprazole prescribed to 31%, followed by Rabeprazole 20%, Esomeprazole (5%) and Lansoprazole (0.7%).

Table 3: Distribution of proton pump inhibitors used in patients.

Proton pump inhibitors No of patients

(N=280)

Percentage

(%)

Omeprazole 122 43%
Pantoprazole 87 31%
Rabeprazole 56 20%
Esomeprazole 13 5%
Lansoprazole 2 0.7

Percentage of Cost Adherence by Patients

Fig 4 shows the percentage of cost adherence by patients using acid suppressant drugs. 182 patients indicated affordable cost this is because among them mostly undergone H.pylori eradication therapy and 81 patients indicated costly remaining 17 patients felt the use of ASMs was cheap.

Fig 4: percentage of cost adherence by patients.

Acid Suppressive Medications for Justified Indications.

Justification for the usage ASMs was based on American society of health system pharmacist (ASHP) therapeutic guidelines on stress ulcer prophylaxis, food and drug administration (FDA) approved and prescribing information and strong literature evidence for the use of ASMs in certain patients.

Fig 5: ratio of justified and unjustified indications.

(Total no of patients (n) =280)

Justified indication (n) = 115 patients

Non-justified indication (n) = 165 patients

Acid Suppressant Medications Prescribed For Justified Indication

Table 4: Acid suppressant medications prescribed for justified indication

Reason No Of Patients N = 280 %
·         NSAIDs prophylaxis(high risk) 8 3
·         Gastic ulcer 2 0.7
·         Duodenal ulcer 4 1.4
·         GERD 7 2.4
·         SUP 12 4.3
·         Helicobacter pylori eradication regimen 82 27.5

Table 4 indicates the list of acid suppressive agents prescribed for non-justified indications. Non justified cases means there is no necessary to prescribe acid suppressant medications for this indication or role of acid suppressant is negligible in this case.

Acid suppressive medications prescribed for non-justified indications

Table 5: Acid suppressive medications prescribed for non-justified indications

Reason for use No of patients

(N =280)

Percentage (%)
      NSAIDS (low risk) 60 21
      Alcoholic 11 4
      Low dose steroid therapy 32 11
      Anaemia 1 0.4
      Epigastic pain (non specific) 50 18
      No reason found 8 3
      Other 3 1

Most Frequently Occurred Side Effect With The Use Of Asms.

Table 6 shows the percentage of side effects occurred with the use of ASMsout of 280 case histories consulted, 33 cases reported mild side effect of ASMs,  mostly all with proton pump inhibitors.

Table 6: Most frequently occurred side effects reported with the use of ASMs

Side Effects No of patients    (N =33)
Bowel change 8
Headache 6
Nausea and vomiting 3
Others 3

Summary of Patients at Different Stages of Their Medical Record Review.

Out of 280 patients, 82 had H.Pylori positive results and 198 had H.Pylori negative result. Among the 82 patients, 60 patients undergone treatment of gastric H.pylori infection with combination of antimicrobials is recognized as the treatment of choice for those patients carrying the infection with peptic ulcer disease.Fig 6: Summary of Patients at Different Stages of Their Medical Record Review

 

H .Pylori Eradication Therapy

Table 7:  The result of H .pylori eradication

Regimen No  of days Number of patients      treated Number

successful

Percent

Success

95% cl
*PPI

Amoxicillin 1gm bid

Nitroimidazole

 

7

 

10

 

3

 

64 %

 

55.6 – 72.4

PPI

Amoxicillin 1 gm bid

Clarithromycin

 

7

 

4

 

1

 

72%

 

64.4– 78.6

**PPI

Tetracycline

Bismuth chelate

Metronidazole

 

7

 

51

 

51

 

100%

 

Erythromycin

PPI

Amoxicillin

 

14

 

8

 

0

 

0%

 

Clarithromycin

Nitroimidazole

Amoxicillin 1 gm bid

 

14

 

2

 

0

 

0%

 

RBC 400 mg bid

Amoxicillin 1gm bid

Clarithromycin 500mg bid

 

7

 

6

 

5

 

94.8%

90.4 -99.2*

**.RBC-A –C was significantly more effective than PPI-A –N, PPI- A-C.

*nonstandard therapy

95% confidence intervals

 

82 received eradication therapy during the period of the study. The remaining were lost during follow up or had inadequate data available. A total of 6 regimens were prescribed. 7 days PPI plus two antibiotic regimen was used in 10 patients. Combination of bismuth colloid and PPI was used in 57 patients and non-standard regimens are used in 10 patients. The results for the individual regimens are shown in table 13. All non standard regimens were unsuccessful.

Changes in Gastric Symptoms Pre-Treatment and Post Treatment.

Improvement of gastric symptoms after the H. Pylori eradication therapy is noted here. Percentage of patients suffering from gastric complaints before, after 6 weeks and after 6 months of therapy is taken into consideration. At baseline more than 50 % of patients had epigastric pain during daytime, heartburn, bloating and belching, 45% complained about epigastric pain during night and 35% of postprandial epigastric pain.

Table 8: changes in Gastric symptoms

Gastrointestinal symptoms Pre-treatment (N) % After 6 Weeks therapy % After 6 months therapy % P value
Epigastric pain during day 29 62 11 26 8 19 <0.001
Epigastric pain during night 22 45 4 9 5 11 <0.001
Epigastrial pain postprandial 17 35 3 7 6 14 <0.01
Pyrosis 29 60 9 20 11 25 <0.001
Nausea 13 28 7 16 8 19 =0.29
Bad breath 10 21 4 10 9 21 <0.1
vomiting 7 15 3 7 1 2 =0.11
Bloating 30 63 15 33 16 37 <0.001
Belching 33 69 21 48 19 46 <0.01
Early satiety 22 46 4 9 11 25 <0.001

*p value <0.001 is significant.

N= no of patients.

After 6 months of therapy, compared to the baseline data, only 19% of patients suffered from epigastric pain during the day (p <0.001), 11% during night (p <0.001) and 14% postprandial (p <0.01), significant improvement could also be reported for heartburn (p <0.001), bloating (p< 0.001), early satiety (p <0.001) and belching(p <0.01). it means that H.pylori eradication therapy almost completely cure the gastric symptoms.In these studies the treatment endpoints are often symptoms and quality of life scales and the intake of acid suppressant drugs during follow up was used as an endpoint

Improvement in Functional Health

COOP/WONCA charts were returned by 48 patients pretreatment, by 46 patients at 6 weeks and by 45 patients at 6 months post treatment. Analysis was based on patients with complete set of symptoms. The mean scores with standard error of each COOP/WONCA category are shown in table 15. The domain social activities (1.4) have low pretreatment scores ,whereas high pre treatment scores are found for pain (2.6) and overall health (3.1). There was a highly significant improvement in functional health for change in health, pain (p < 0.001) and overall health (p <0.01). No significance was found for physical fitness or social activities.

Table 9: Improvement in functional after H. pylori eradication therapy.

Functional health

Status

Pretreatment Post treatment P-Values
6 Weeks

therapy

6 Months

Therapy

Mean SD/SE
Mean SD/SE Mean SD/SE
Physical fitness 2.6 1+_0.577 2.4 1+_0.177 2.5 1+-0.22 =0.43
Social activities 1.4 0.816+_0.33 1.3 0.78+_0.1 1.4 0.57+_0.12 =0.88
Daily activities 1.9 0.83+_0.37 1.5 0.816+_0.38 1.5 0.721+_0.1 *<0.05
Change in health 2.9 0.57+_7.33 2.2 0.7+_0.11 2.7 0.816+_0.33 **<0.001
Overall health 3.1 0.1+_0.477 2.6 1+_0.24 2.6 1+_0.588 <0.01
Pain 2.6 1+_0.577 1.8 0.8+_0.334 1.6 0.816+_0.1 **<0.001
N 48 46 45

**P value <0.001 is extremely significant.

*p value < 0.05 is significant.

N = Total no of patients.

SE = standard error.

DISCUSSION

These studies confirmed that the acid suppressant drugs use was more in males than in women. In the present study it was shown that the acid suppressant drug use increases with increase in age. Current study shows that Step-down therapy is preferred approach for most cases.

Out of 280 case history, proton pump inhibitors is found to be most widly used ASDs, As presented at the 2012 society of critical care medicine Annual Congress, updated guidelines, it is expected that H2RAs will be recommended as first line therapy and that use of PPIs will be reserved for those who have failed or cannot tolerate a H2RAs.Sometimes physician will prescribe more than one acid suppressants at a time.

There is a possible link between vitamin B12 deficiency and acid inhibiting medication; it has potentially serious medical complications if undiagnosed. Left un treated vitamin B12 deficiency lead to dementia, neurological damage and anemia, while giving ASDs therapy hemoglobin monitoring is essential.

The current study found that quadruple therapy is highly effective, well –tolerated anti –Helicobacter regimen in primary health care setting.  General practitioners to review their ASMs prescribing pattern to treat the in appropriate indications and prophylaxis uses.

References

  • Abu-Mahfouz MZ, Prasad VM, Santograde P, et al. Helicobacter pylori recurrence after successful eradication: 5-year follow-up in the United States.Am J Gastroenterol 1997; 92:20 25
  • Bell GD, Powell KU, Burridge SM, et al. Reinfection or recrudescence after apparently successful eradication of Helicobacter pylori infection: implications for treatment of patients with duodenal ulcer disease. QJM 1993; 86:375-82.
  • Borody T, Andrews P, Mancuso N, et al. Helicobacter pylori reinfection 4 years post-eradication. Lancet 1992; 339:1295
  • Chong E, Ensom MHH. Pharmacotherapy 2003; 23: 460-71
  • Prescribing Information. Plavix (clopidogrel). Bridgewater, NJ: Bristol- Myers Squibb/ Sanofi Pharmaceutical science. 1992
  • McColl KEL, Murray LS, Gillen D. Omeprazole and accelerated onset of atrophic gastritis. Gastroenterology 2000; 118: 239
  • FDA Drug Safety Communication: Clostridium difficile-associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs).
  • http://www.fda.gov/Drugs/DrugSafety/ucm290510.htm. Accessed June 8, 2012.
  • http://www.medicaldaily.co/acid suppressing medications-linked-vitamin b12 deficiency