Bronchial Hyper-responsiveness in Reflux Cough

• Sponsor: Hull University Teaching Hospitals NHS Trust (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00668317
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 40
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study aim is to determine the effect of 8 weeks of anti-reflux treatment (full acid suppression) on bronchial hyper-responsiveness and whether there is a symptomatic improvement.

Condition or Disease	Intervention/Treatment	Phase
Cough	Drug: Omeprazole; Drug: Ranitidine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Health Services Research
• Official Title: An 8 Week Non-selected Cohort Study to Investigate Whether the Treatment of Reflux Induced Cough Alters Associated Bronchial Hyper-responsiveness
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Other: omeprazole and ranitidine 20 mg oralomeprazole oral tablet twice daily and ranitidine 300 mg oral tablet once daily nocte	Drug: Omeprazole; 20 mg BD tablet 8 weeks duration; Other Names: Losec ; Drug: Ranitidine; 300 mg od nocte tablet 8weeks duration; Other Names: Zantac

Outcome Measures

Primary Outcome Measures

1. Change in Methacholine Sensitivity [baseline and 8 weeks]

   Concentration of methacholine (mg/ml) at which participants forced expired volume in 1 sec (FEV1) is reduced by 20% (the provocation concentration of methacholine causing a 20% fall in FEV1-PC20). To measure if there is a significant difference in PC20 recorded at baseline to that recorded following 8 weeks treatment with omeprazole and ranitidine

Secondary Outcome Measures

1. Improvement in Cough Symptoms Measured Using Leicester Cough Questionnaire [8 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Positive methacholine challenge test PC20 less than 4mg/ml (Can be previously documented in patients notes within last 4weeks)

• Written informed consent

• Patients with a history of chronic cough (at least 3 months duration), and associated symptoms of gastro-oesophageal reflux

• Male and female subjects of at least 18 yrs of age

• Subjects able to perform satisfactory FEV1 manoeuvres

• Subjects able to understand the study and co-operate with the study procedures

• Subjects who consent to their general practitioner (GP) being informed of their study participation

Exclusion Criteria:

• has had a heart attack in the last three months

• suffers from angina, hypertension or ischaemic heart disease

• has epilepsy for which he/she is taking medication

• FEV1< 60% predicted

• FEV1<1.6L

• Female subjects who are pregnant, or lactating, or who are of child bearing potential but are not using contraceptive measures

• Suffering from any concomitant disease which may interfere with study procedures or evaluation.

• A lower respiratory tract infection 4 weeks prior to entry on to study

• Participation in another study (use of investigational product) within 30 days preceding entry on to study.

• Alcohol or drug abuse

• Use of opiates to treat cough 1 week prior to enrollment

• Subjects who are taking Angiotensin Converting Enzymes (ACE) inhibitors.

• Subjects who have significant pathology on most recent chest X-Ray.

• Inability to understand the procedures and the implications of a challenge test

• Patients already taking or have taken in last 4 weeks PPI and H2 receptor antagonist (full acid suppression treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trials Unit , Cardiovascular and respiratory studies, Castle Hill Hospital	Cottingham	East Yorkshire	United Kingdom	HU16 5JQ

Sponsors and Collaborators

• Hull University Teaching Hospitals NHS Trust

Investigators

• Principal Investigator: Alyn H Morice, Professor, Hull University Teaching Hospitals NHS Trust

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Publication Link

Publications

• Morice AH, Kastelik JA, Thompson R. Cough challenge in the assessment of cough reflex. Br J Clin Pharmacol. 2001 Oct;52(4):365-75. Review.

• Responsible Party: Hull University Teaching Hospitals NHS Trust
• ClinicalTrials.gov Identifier: NCT00668317
• Other Study ID Numbers: 2006-004102-13
• First Posted: Apr 29, 2008
• Last Update Posted: Jul 23, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Hull University Teaching Hospitals NHS Trust: Hyper-responsiveness, reflux cough
• Additional relevant MeSH terms: Cough; Bronchial Hyperreactivity; Omeprazole; Ranitidine; Ranitidine bismuth citrate

Study Results

Participant Flow

Recruitment Details	Patients recruited at the cough clinic at castleHill Hospital
Pre-assignment Detail	Patients had to have a positive methacholine challenge, and reflux associated chronic cough

Arm/Group Title	Antacid Therapy
Arm/Group Description	Therapy with omeprazole 20 mg BD and Ranitidine 300mg od nocte
Period Title: Overall Study
STARTED	5
COMPLETED	3
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Antacid Therapy
Arm/Group Description	Therapy with omeprazole 20 mg BD and Ranitidine 300mg od nocte
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.8 (8.53)
Sex: Female, Male (Count of Participants)
Female	4 80%
Male	1 20%
Region of Enrollment (participants) [Number]
United Kingdom	5 100%

Outcome Measures

1. Primary Outcome

Title	Change in Methacholine Sensitivity
Description	Concentration of methacholine (mg/ml) at which participants forced expired volume in 1 sec (FEV1) is reduced by 20% (the provocation concentration of methacholine causing a 20% fall in FEV1-PC20). To measure if there is a significant difference in PC20 recorded at baseline to that recorded following 8 weeks treatment with omeprazole and ranitidine
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

All subjects recruited with efficacy data recorded after week T0 will be included in the ITT population for analysis. Assuming a within subject standard deviation(for change in PC20) of no more than 2.71 units, 30 subjects are sufficient to provide 80% power to detect a treatment difference of 1.8 units using a 5% two sided significance test

Arm/Group Title	Omeprazole and Ranitidine
Arm/Group Description	Therapy with omeprazole 20 mg twice a day (BD) and Ranitidine 300mg once a day (od) at night (nocte)
Measure Participants	3
Mean (Standard Deviation) [mg/ml]	0.598 (0.479)

2. Secondary Outcome

Title	Improvement in Cough Symptoms Measured Using Leicester Cough Questionnaire
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	8 week
Adverse Event Reporting Description	data collected at each visit of the study
Arm/Group Title	Antacid Therapy
Arm/Group Description	Therapy with omeprazole 20 mg BD and Ranitidine 300mg od nocte
All Cause Mortality
	Antacid Therapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Antacid Therapy
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	Antacid Therapy
	Affected / at Risk (%)	# Events
Total	0/3 (0%)

Limitations/Caveats

[Not Specified]

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.