Symptomatic Relief of Acute Dyspeptic Pain in Emergency Department With Pantoprazole

• Sponsor: Chulalongkorn University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01281501
• Collaborator: (none)
• Enrollment: 87
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 9.7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the immediate synergistic effect on the relief of severe acid-related dyspeptic pain by adding intravenous pantoprazole to the combination of oral antacid and antispasmodic agent (the conventional treatment).

Condition or Disease	Intervention/Treatment	Phase
Dyspepsia; Emergency; Pain	Drug: Normal saline; Drug: Pantoprazole; Drug: Oral antacid; Drug: Hyoscine butylbromide	Phase 4

Detailed Description

Acid-related dyspepsia is common among the population. Number of these patients may have so severe symptoms that can lead them to the emergency department. Mixtures of antacid and antispasmodic were widely used over decades to relieve this acute pain with moderate, yet questionable, improvement in pain score. Proton pump inhibitors (PPIs), the novel acid-lowering agents, are undoubtedly effective to reduce acid secretion and control dyspeptic symptoms in short-term and long-term duration. To our knowledge, no previous study was conducted to evaluate the efficacy of such agents on immediate pain relief in patients with severe dyspeptic symptoms in emergency care. Clinically, they are frequently used to treat this circumstance in an unofficial manner since intravenous proton pump inhibitor alone is not yet considered as a well-approved indication to alleviate such condition. Pantoprazole, a proton pump inhibitor, reaches its peak serum concentration within one hour and its acid-lowering effect occurred within first hour following a single intravenous infusion. Thus, it theoretically has rapid onset and prolonged action on acid reduction. Our primary aim of the study is to evaluate the immediate effect of intravenous pantoprazole in addition to the combination of oral antacid and antispasmodic agent (the conventional regimen) on the relief of severe acid-related dyspeptic pain.

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled Trial of Adding Intravenous Pantoprazole to Conventional Treatment for the Immediate Relief of Dyspeptic Pain
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Conventional Oral antacid, 20 mg of intravenous hyoscine butylbromide, normal saline	Drug: Normal saline; 10 ml of 0.9% sodium chloride solution; Drug: Oral antacid; 30 ml of oral antacid (1.32 grams of aluminum hydroxide, 0.72 grams of magnesium hydroxide); Other Names: Antacid ; Drug: Hyoscine butylbromide; 20 mg of intravenous hyoscine butylbromide; Other Names: Buscopan
Experimental: Pantoprazole Oral antacid, 20 mg of intravenous hyoscine butylbromide, 80 mg of intravenous pantoprazole	Drug: Pantoprazole; 80 mg of intravenous pantoprazole; Other Names: Controloc (Protonix) ; Drug: Oral antacid; 30 ml of oral antacid (1.32 grams of aluminum hydroxide, 0.72 grams of magnesium hydroxide); Other Names: Antacid ; Drug: Hyoscine butylbromide; 20 mg of intravenous hyoscine butylbromide; Other Names: Buscopan

Outcome Measures

Primary Outcome Measures

1. Pain Scores on the 100-millimeter Visual Analog Scale (VAS) at 1 Hour After Treatment [1 hour after treatment]

   Post-treatment VAS will be consecutively measured every 15 minutes until 1 hour after treatment. Minimal and maximal VAS score of every measurement is 0 to 100 millimeters. VAS scores at 1 hour after treatment were the primary outcome measurement. The patients who had <50% decrement between pre- and 1-hour post-treatment VAS or post-treatment scores > 40 millimeters were defined as "Non-responders"(worse outcome). In the same way, those who had ≥ 50% decrement between pre- and 1-hour post-treatment VAS and post-treatment scores≤ 40 millimeters were defined as "Responders" (good outcome).

Secondary Outcome Measures

1. Number of Participants in the Predefined "Responders" [pretreatment and 1 hour after treatment]

   "Responders" define the participants who have ≥ 50% decrease in post-treatment pain scores compared with the pre-treatment evaluation and also have the post-treatment scores ≤ 40 at the end of the study.

2. Number of Participants in the Predefined "Non-responders" [pretreatment and 1 hour after treatment]

   "Non-responders" defined the participants who had < 50% decrease in post-treatment VAS compared with pre-treatment evaluation or post-treatment scores > 40 at the end of the study.

3. Number of Participants With Adverse Effect [1 hour after treatment]

   The adverse effects include blurred vision, dry mouth, dizziness, headache, palpitation and diarrhea.

4. Number of Participants That Have Overall Satisfaction on the Treatment [1 hour after treatment]

   The satisfaction will be assessed by a simple, self-reported yes/no question.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• clinical diagnosis of acid-related dyspepsia

• age 15 to 50 years

Exclusion Criteria:

• pre-treatment 100-millimeter linear Visual Analog Scale (100-mm VAS) pain scores less than 5.0

• known cases of malignancies or terminal illnesses

• known cases of major medical problems

• allergic to studied drugs

• contraindicated to hyoscine butylbromide (glaucoma, myasthenia gravis, paralytic ileus, pyloric stenosis, prostatic enlargement, porphyria)

• received acid antisecretory agents (proton pump inhibitors or histamine-2 receptor antagonists), antispasmodic agents, alcoholic consumption, nonsteroidal anti-inflammatory drugs, aspirin and steroids within 5 days or oral antacids within 4 hours prior to the visit

• receiving clopidogrel, statins, iron therapies, warfarins, antiretroviral agents, which may have serious drug interaction with the proton pump inhibitors

• receiving drugs that have strong anticholinergic activities (e.g. acetylcholinesterase inhibitors for Parkinson's or Alzheimer diseases, antihistamines, antispasmodic agents, antipsychotics, skeletal muscle relaxants, tricyclic antidepressants) or decongestants, which may have serious drug interaction with hyoscine butylbromide

• suspected other alternative diagnoses (e.g. gut obstruction, biliary colic, pancreatitis, hepatitis or localized hepatobiliary infections, etc.)

• pregnancy or breast-feeding participants

• did not comprehend the Visual Analog Scale (VAS) evaluation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emergency Medicine Unit, King Chulalongkorn Memorial Hospital	Patumwan	Bangkok	Thailand	11130

Sponsors and Collaborators

• Chulalongkorn University

Investigators

• Principal Investigator: Khrongwong Musikatavorn, MD, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Khrongwong Musikatavorn, MD., Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital., Chulalongkorn University
• ClinicalTrials.gov Identifier: NCT01281501
• Other Study ID Numbers: 619/2010
• First Posted: Jan 24, 2011
• Last Update Posted: Sep 18, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Khrongwong Musikatavorn, MD., Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital., Chulalongkorn University: Dyspepsia; Emergency treatment; Pantoprazole; Antacid; Pain measurement
• Additional relevant MeSH terms: Emergencies; Dyspepsia; Scopolamine; Pantoprazole; Anti-Ulcer Agents; Antacids; Butylscopolammonium Bromide

Study Results

Participant Flow

Recruitment Details	Enrollment began in January, 1 2011 and finished at the end October, 31 2011 in the Emergency Department of King Chulalongkorn Memorial Hospital
Pre-assignment Detail	We analyzed the data for all enrolled patients with the intention-to-treat principles.

Arm/Group Title	Conventional	Pantoprazole
Arm/Group Description	Oral antacid, 20 mg of intravenous hyoscine butylbromide, normal saline	Oral antacid, 20 mg of intravenous hyoscine butylbromide, 80 mg of intravenous pantoprazole
Period Title: Overall Study
STARTED	44	43
COMPLETED	44	43
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Conventional	Pantoprazole	Total
Arm/Group Description	Oral antacid, 20 mg of intravenous hyoscine butylbromide, normal saline	Oral antacid, 20 mg of intravenous hyoscine butylbromide, 80 mg of intravenous pantoprazole	Total of all reporting groups
Overall Participants	44	43	87
Age (Count of Participants)
<=18 years	1 2.3%	3 7%	4 4.6%
Between 18 and 65 years	43 97.7%	40 93%	83 95.4%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.8 (8.1)	29.4 (9.2)	29.6 (8.6)
Sex: Female, Male (Count of Participants)
Female	33 75%	35 81.4%	68 78.2%
Male	11 25%	8 18.6%	19 21.8%
Region of Enrollment (participants) [Number]
Thailand	44 100%	43 100%	87 100%
Pretreatment 100-millimeter visual analog scale (VAS) scores (millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeters]	64 (13)	64 (16)	64 (14)

Outcome Measures

1. Primary Outcome

Title	Pain Scores on the 100-millimeter Visual Analog Scale (VAS) at 1 Hour After Treatment
Description	Post-treatment VAS will be consecutively measured every 15 minutes until 1 hour after treatment. Minimal and maximal VAS score of every measurement is 0 to 100 millimeters. VAS scores at 1 hour after treatment were the primary outcome measurement. The patients who had <50% decrement between pre- and 1-hour post-treatment VAS or post-treatment scores > 40 millimeters were defined as "Non-responders"(worse outcome). In the same way, those who had ≥ 50% decrement between pre- and 1-hour post-treatment VAS and post-treatment scores≤ 40 millimeters were defined as "Responders" (good outcome).
Time Frame	1 hour after treatment

Outcome Measure Data

Analysis Population Description

All enrolled patients were analyzed with the intention-to-treat principles.

Arm/Group Title	Conventional	Pantoprazole
Arm/Group Description	Oral antacid, 20 mg of intravenous hyoscine butylbromide, normal saline	Oral antacid, 20 mg of intravenous hyoscine butylbromide, 80 mg of intravenous pantoprazole
Measure Participants	44	43
Mean (Standard Deviation) [millimeter]	17 (24)	19 (23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Conventional, Pantoprazole
	Comments	Null hypothesis is that the treatment with pantoprazole arm is not different in immediate relief of acute, severe dyspeptic pain compared with conventional arm.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -12.7 to 7.4
	Parameter Dispersion	Type: Standard Deviation; Value: 5.0
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants in the Predefined "Responders"
Description	"Responders" define the participants who have ≥ 50% decrease in post-treatment pain scores compared with the pre-treatment evaluation and also have the post-treatment scores ≤ 40 at the end of the study.
Time Frame	pretreatment and 1 hour after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conventional	Pantoprazole
Arm/Group Description	Oral antacid, 20 mg of intravenous hyoscine butylbromide, normal saline	Oral antacid, 20 mg of intravenous hyoscine butylbromide, 80 mg of intravenous pantoprazole
Measure Participants	44	43
Number [participants]	36 81.8%	32 74.4%

3. Secondary Outcome

Title	Number of Participants in the Predefined "Non-responders"
Description	"Non-responders" defined the participants who had < 50% decrease in post-treatment VAS compared with pre-treatment evaluation or post-treatment scores > 40 at the end of the study.
Time Frame	pretreatment and 1 hour after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conventional	Pantoprazole
Arm/Group Description	Oral antacid, 20 mg of intravenous hyoscine butylbromide, normal saline	Oral antacid, 20 mg of intravenous hyoscine butylbromide, 80 mg of intravenous pantoprazole
Measure Participants	44	43
Number [participants]	8 18.2%	11 25.6%

4. Secondary Outcome

Title	Number of Participants With Adverse Effect
Description	The adverse effects include blurred vision, dry mouth, dizziness, headache, palpitation and diarrhea.
Time Frame	1 hour after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Number of Participants That Have Overall Satisfaction on the Treatment
Description	The satisfaction will be assessed by a simple, self-reported yes/no question.
Time Frame	1 hour after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conventional	Pantoprazole
Arm/Group Description	Oral antacid, 20 mg of intravenous hyoscine butylbromide, normal saline	Oral antacid, 20 mg of intravenous hyoscine butylbromide, 80 mg of intravenous pantoprazole
Measure Participants	44	43
Number [participants]	34 77.3%	34 79.1%

Adverse Events

Time Frame	1 hour
Arm/Group Title	Conventional		Pantoprazole
Arm/Group Description	Oral antacid, 20 mg of intravenous hyoscine butylbromide, normal saline		Oral antacid, 20 mg of intravenous hyoscine butylbromide, 80 mg of intravenous pantoprazole
All Cause Mortality
	Conventional		Pantoprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Conventional		Pantoprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Conventional		Pantoprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/44 (70.5%)		30/43 (69.8%)
Cardiac disorders
palpitation	2/44 (4.5%)	2	0/43 (0%)	0
Eye disorders
transient blurred vision	22/44 (50%)	22	29/43 (67.4%)	29
Gastrointestinal disorders
dry mouth	12/44 (27.3%)	12	6/43 (14%)	6
nausea	2/44 (4.5%)	2	0/43 (0%)	0
Nervous system disorders
dizziness	3/44 (6.8%)	3	3/43 (7%)	3
headache	2/44 (4.5%)	2	0/43 (0%)	0

Limitations/Caveats

1. This was a small, single-centered study. 2. Exaggerated self-evaluation of the patients' pain score and the physician's expectation of a "good outcome" may also have biased the report. 3. The short-term recurrence of the pain was not studied.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.