Methodology

Study Design

Open comparative clinical study of Esomeprazote versus Rabeprazole in patients with GERD and its long term follow up.

Materials and methods

This study was carried out after obtaining the informed consent from the patients for the drug trial.

Study population

Total no. of patients – 140

Sex – Both sexes

Age group — 18 to 58 years.

Drug Selection

Either Esomeprazole 40 mg orally or Rabeprazole 20 mg;given once daily before breakfast for the initial 8 weeks.

Patient Evaluation

Baseline symptoms like heart burn, regurgitation and abdominal bloat were assessed on a 4 point clinical scale from 0 (no symptoms) to 3 (severe symptoms) and endoscopic grading (Grade 0 — normal mucosa, Grade 1— erythema or hyperemia of the oesophageal mucosa, Grade 2 — superficial ulceration or erosion involving less than 10% of the surface of the distal 5 cm of oesophageal mucosa, Grade 3 — superficial ulceration or erosion involving less than 10 to 50 % of the surface of the distal 5 cm of oesophageal mucosa and Grade 4 — deep ulceration anywhere in the oesophagus or confluent erosions involving more than 50 % of the mucosa’ surface of the distal 5 cm of oesophagus).

Exclusion Criteria

Patients who were pregnant or breast feeding.

Patients with oesophageal stricture or gastric outlet obstruction.

Post operative stomach.

Patients with malignancy.

Severe systemic diseases.

Patients on long term NS AIDs.

Known hypersensitivity to these drugs.

Treatment and follow up

Phase I

Symptoms and endoscopic findings were graded on a scale from Grade 1 to 4 as mentioned before both at baseline before starting drug therapy and after 8 weeks Any complications or side effects of the drugs were also recorded and the patients were instructed to report within 48 hours in such situations.

Phase II

After discontinuation of therapy, these patients were followed up for the next 24 months  for symptom analysis. These patients were requested to report at the end of 6th month.  12th month, 18^th month and 24^th month and their symptoms were recorded.

Phase III

During the follow up, if the symptoms recur, the grading of symptoms were recorded and the patients were restarted on the same drugs they were earlier on at the start of the trial. The drugs were given for the next 8 weeks and the efficacy recorded. Any minor side effects, which do not require discontinuation of therapy, were also carefully recorded. UGI endoscopy was repeated in whom satisfactory relief was not obtained at the end of study period.

Criteria for Evaluation

The severity is assessed both clinically and endoscopically.

Clinical Assessment

Grade 0 — Complete symptom resolution.

Grade 1 — Improvement of symptoms, but not total resolution.

Grade 2 — No change of symptoms.

Grade 3 — Worsening of symptoms.

Endoscopic Assessment

Grade 0 — Complete healing. Grade I — No visible macroscopic erosion, but erythema present. Grade II — Superficial ulceration and erosion involving < 10% of mucosal surface. Grade III — Ulceration or erosion involving 50% of mucosal surface at the distal 5 cm. Grade IV — Deep ulceration in the distal 5 cm of oesophagus.

Withdrawal of Patients from the Study

Request of the patient.

Discretion of the principal investigator on clinical grounds.

Patient lost for follow up.

Adverse side effects.

Results

Demographic Data

Total no. of patients — 140.

Age group — 18 — 58 years.

Sex — both sexes.

Rabeprazole group — 70 patients.

Esomeprazole group — 70 patients.

Phase I Trial

Symptom Analysis

There was significant decrease in the clinical severity of symptoms in both the groups, 70% in Esomeprazole group and 84% in Rabeprazole group at the end of 2″ week. At the end of 8th week 90% relief was noted with Esomeprazole and 92% relief was noted in Rabeprazole group.

Figure 1   Click here to View figure

Healing Rate of Oesophagitis by Endoscopy

Table 1

UGI endoscopy revealed 84% healing rate by Esomeprazole group and 82% healing rate in Rabeprazole group.

Tolerability

In Esomeprazole group 7% and 5.6% in Rabeprazole group had bearable side effects like mild giddiness and head ach. No body had severe side effects as to warrant stoppage of treatment.

Phase II

During the post treatment follow up in the next 24 months following is the observation made in symptom analysis.

Clinical Improvement of Symptoms

Figure 2   Click here to View figure

At the end of 24 months 78% in Esomeprazole group and 64% in Rabeprazole group . were symptom free.

Phase III

In patients who had recurrence of symptoms, the same drugs were reintroduced. In the Esomeprazole group 11 patients and in the Rabeprazole group 24 patients had recurrence of symptoms. The following observations were made in them.

Table 2

No relief of symptoms was noted in 8% of patients in the Esomeprazole group and 17% of patients in the Rabeprazole group. Resistance to therapy in both the groups was associated with large hiatus hernia and in elderly age group.

Discussion

Esomeprazole has shown, in recent trials to be more effective in control of intragastric pH, higher and more predictable ulcer healing rate and maintenance of virtually all the patients in remission, when compared to Rabeprazole. The metabolism¹ and pharinacokinetic profile² of the PPI polymorphism plays an additional role in the therapeutic effectiveness of PPI during the treatment of acid related disorders. PPI act by binding covalently to the aminoacid cystein 813 present in the primary binding site in the proton pump in the luminal surface of the gastric parietal cells. This results in the irreversible inhibition of acid secretion. The acid secretion resume only after recruititjg newly synthesized proton pumps from the Golgi apparatus. Esomeprazole is more potent than Rabeprazole in long term treatment of GERD.^5,6

Conclusion

Oral Esomeprazole is as effective as Rabeprazole in GERD patients during short term therapy.⁷ Symptomatic relief was sustained in 78% of patients in Esomeprazole group when compared to 64% in Rabeprazole group. Resistance to treatment occurs in 8% of patients in Esomeprazole group, when compared to 18% in Rabeprazole group. when  reintroduced in patients with recurrence of symptoms. Esomeprazole has the longest area under the curve and gives acid suppression for the longest period of time⁸ So it is very effective in the long term treatment of GERD patients. Side effects are insignificant with both drugs.

References

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