Methods

Randomised clinical trial

Participants

Country: Canada.

Number randomised: 104

Post‐randomisation drop‐outs: 21 (20.2%)

Revised sample size: 83

Average age: 43 years

Females: 49 (59%)

Barretts oesophagus: not stated

Hiatus hernia: not stated

Body mass index: not stated

Inclusion criteria

1. Men or women aged 18 to 70 years old with chronic reflux symptoms requiring long‐term therapy.

2. Prior long‐term treatment with proton pump inhibitor (minimum duration 1 year) with expected future duration of at least two more years.

3. Symptoms controlled before the study, defined as a GERD symptom score of less than 18 and a score of 70 or more on 1‐100 Global Visual Analog Scale (VAS) (on medication).

4. Percentage of acid reflux in 24 hours exceeding 4% at baseline (off medication).

5. Positive Bernstein test at baseline.

6. Willingness to adhere to randomized treatment, with availability for three years of follow‐up.

7. Ability to answer self‐administered and interviewer‐administered questions in English.

8. Signed informed consent.

Exclusion criteria

1. Aperistaltic oesophagus.

2. Severe cardiac, respiratory, hematologic, or other disease constituting an unacceptable surgical risk in the investigator’s opinion.

3. Previous gastric, oesophageal, or antireflux surgery.

4. Malignancy within the past year, with the exception of basal cell carcinoma.

5. Pregnancy or an intention to become pregnant in the next three years.

Interventions

Participants were randomly assigned to two groups.
Group 1: surgery (n = 43)
Further details: Laparoscopic Nissen fundoplication
Group 2: medical treatment (n = 40)
Further details: Same PPI dose as previous treatment.

Outcomes

The outcomes reported were health‐related quality of life, GERD‐specific quality of life, and adverse events.

Notes

Reasons for post‐randomisation drop‐outs: nine: surgical treatment (one did not follow received allocation; eight lost to follow‐up) and 12: medical treatment (two did not follow received allocation; 10 lost to follow‐up).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The uniform random integers, 0 through 9, were generated in Minitab 12 (Minitab Inc, State College, PA) for each stratum….. The groups of 16 for blocks of 2 or 4 were generated at random, using single‐digit random numbers, odd being SC (surgery, control) and even being CS".

Allocation concealment (selection bias)

Low risk

Quote: "To this extent the research assistants checking the eligibility were not exposed to the continuing randomization list".

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: "Consequently, this study did not have blinded implementation of the treatment arms".

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Quote: "Consequently, this study did not have blinded implementation of the treatment arms".

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: There were post‐randomisation drop‐outs.

Selective reporting (reporting bias)

Low risk

Comment: Important outcomes were reported.

Other bias

Low risk

Quote: "Supported by grants from Canadian Institute of Health Research and Ontario Ministry of Health and Long‐term Care".

Methods

Randomised clinical trial

Participants

Country: United Kingdom

Number randomised: 357

Post‐randomisation drop‐outs: not stated

Revised sample size: 357

Average age: 46 years

Females: 121 (33.9%)

Barretts oesophagus: not stated

Hiatus hernia: not stated

Body mass index: 29

Inclusion criteria

1. More than 12 months’ symptoms requiring maintenance treatment with a proton pump inhibitor (or alternative) for reasonable control.

2. Endoscopic or 24 hour pH monitoring evidence of GORD, or both.

3. Suitable for either policy (including American Society of Anesthesiologists (ASA) grade I or II) and the recruiting doctor was uncertain which management policy to follow.

Exclusion criteria

1. Morbid obesity (BMI > 40)

2. Barrett’s oesophagus of more than 3 cm or with evidence of dysplasia.

3. Para‐oesophageal hernia

4. Oesophageal stricture

Interventions

Participants were randomly assigned to two groups.
Group 1: surgery (n = 178)
Further details: Laparoscopic fundoplication as per surgeon preference.
Group 2: medical treatment (n = 179)
Further details: Medical treatment as per local protocol.

Outcomes

The outcomes reported were health‐related quality of life, GORD‐specific quality of life, proportion with heartburn, reflux, and dysphagia.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Random allocation was organised centrally by a secure system, using a computer‐generated sequence, stratified by clinical site, with balance in respect of age (18 ‐ 49 or ≥ 50), sex (men or women), and BMI (≤ 28 or > 29) secured by minimisation".

Allocation concealment (selection bias)

Low risk

Quote: "Staff in the central trial office entered details of participants on the secure database, then notified participants and respective clinical sites of their allocation".

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: "There was no subsequent blinding".

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Quote: "There was no subsequent blinding".

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: An intention‐to‐treat analysis was performed.

Selective reporting (reporting bias)

High risk

Comment: Treatment‐related complications were not reported adequately.

Other bias

Low risk

Quote: "This study was funded by the NIHR Health Technology Assessment Programme (as part of project No 97/10/99)".

Methods

Randomised clinical trial

Participants

Country: Europe

Number randomised: 554

Post‐randomisation drop‐outs: not stated

Revised sample size: 554

Average age: 45 years

Females: 156 (28.2%)

Barretts oesophagus: 60 (10.8%)

Hiatus hernia: not stated

Body mass index: not stated

Inclusion criteria

1. Adults aged 18–70 years with confirmed GORD, with or without Barret's oesophagus.

2. History of chronic reflux oesophagitis (> 6 months) or chronic symptomatic GORD (> 6 months) with pathological 24‐h pH metry, according to local standards, and a requirement for long‐term acid suppressive therapy.

3. All patients were required to have had pH monitoring and manometry within 12 months prior to randomization.

4. All had to be considered suitable for both surgical treatment and for long‐term management with a PPI (esomeprazole).

5. Capable of completing quality‐of‐life questionnaires.

Exclusion criteria

1. Primary need for surgery (e.g. for paraoesophageal hernia or failure of medical therapy to control symptoms adequately) was not eligible to be recruited.

2. Required PPI treatment for diseases other than GORD.

3. History of oesophageal, gastric, or duodenal surgery or who had other diseases that might have a negative impact on their subsequent treatment within the study.

Interventions

Participants were randomly assigned to two groups.
Group 1: surgery (n = 288)
Further details: Laparoscopic Nissen fundoplication
Group 2: medical treatment (n = 266)
Further details: Esomeprezole 20 mg once daily increased to maximum of 40 mg once daily or 20 mg twice daily.

Outcomes

The outcomes reported were GORD‐specific quality of life, proportion with heartburn, reflux, dysphagia and adverse events.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: This information was not available.

Allocation concealment (selection bias)

Unclear risk

Comment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: Patients undergoing medical treatment did not have sham surgery.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Comment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: An intention‐to‐treat analysis was performed.

Selective reporting (reporting bias)

Low risk

Comment: Important outcomes were reported.

Other bias

High risk

Quote: "This study was funded by Astrazeneca, Mölndal, Sweden".

Methods

Randomised clinical trial

Participants

Country: United Kingdom

Number randomised: 217

Post‐randomisation drop‐outs: 51 (23.5%)

Revised sample size: 166

Average age: 48 years

Females: not stated

Barretts oesophagus: not stated

Hiatus hernia: not stated

Body mass index: not stated

Inclusion criteria

1. Symptoms of GORD for at least six months.

2. Three months minimum of proton pump inhibitor maintenance therapy.

3. Proven reflux (as measured by 24 hour pH/manometry).

4. No preference for either surgical or medical treatment.

5. Between 16 and 70 years old.

6. Fit for surgery.

Exclusion criteria

1. Significant oesophageal dysmotility.

2. Morbid obesity (BMI = 35).

3. Refused pH testing and manometry.

Interventions

Participants were randomly assigned to two groups.
Group 1: surgery (n = 80)
Further details: Laparoscopic Nissen fundoplication
Group 2: medical treatment (n = 86)
Further details: Proton pump inhibitor adjusted to symptom control.

Outcomes

The outcomes reported were health‐related quality of life and gastrointestinal quality of life.

Notes

Reasons for post‐randomisation drop‐outs: Lost‐to follow‐up.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: This information was not available.

Allocation concealment (selection bias)

Unclear risk

Comment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: Patients undergoing medical treatment did not have sham surgery.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: There were post‐randomisation drop‐outs.

Selective reporting (reporting bias)

High risk

Comment: Treatment‐related complications were not reported adequately.

Other bias

High risk

Quote: "This study was funded partly by Janssen Pharmaceuticals relating to physiology studies at the Norfolk Physiology Laboratory in conjunction with their GI Partnership Scheme. Yvette Sharpe performed most of these studies under the supervision of R.L. B.D., D.M. and B. K. were funded partly by Ethicon Endosurgery, UK".