Abdominal Pain, Surgical Adhesions
Conditions
Keywords
abdominal pain, surgical adhesions
Brief summary
The purpose of this study is to evaluate if pregabalin demonstrates significant reduction in abdominal pain from adhesions.
Detailed description
The study will be prospective, double-blinded and randomized. The study will run for 12 weeks. During the first 7 weeks there will be 2 groups in the study with subjects receiving a placebo or the study drug. During the last 4 weeks of the study, all subjects will be offered the study medication, pregabalin. The primary outcome measure will be pain relief documented by a 2-point change on the Likert pain scale with a secondary pain measure of sleep interruption.
Interventions
DRUGPregabalin 75 or 150 mg BID for 7 weeks followed by open label pregabalin 150 mg BID for 4 weeks
First 7 weeks 75 or 150 mg of pregabalin po BID. Start at 75 mg and increase to 150 mg po BID if no improvement after 3 days and treat for 7 weeks. Followed by open label pregabalin for 4 weeks at 150 mg BID
DRUGPlacebo first followed by open label pregabalin
Look alike placebo 75 mg po BID and increase to 150 mg BID after 3 days if no improvement for 7 weeks. Open label pregabalin 150 mg BID for last 4 weeks of study.
Sponsors
Pfizer
Henry Ford Health System
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blinding was done to ensure minimum bias. Clinicians were not involved in the randomization process. Patients and clinicians were blinded to the identity of the drug as a look alike placebo was used. The randomization code was was maintained by the research assistant and kept in a locked file cabinet. Separated individuals generated the allocation sequence. The blind was maintained until all the decisions regarding data evaluability were made or in the event of a serious adverse event.
Intervention model description
Patients were evaluated for the study and were entered into the study if they had documented abdominal adhesions and a daily pain score of 40 mm on a visual assessment scale and 4 on an eleven point Likert scale (0 none and 10 most pain). Patients were randomly assigned to active drug or look alike placebo for 7 weeks followed by an open label phase in which all patients received active drug pregabalin 300 mg daily for 4 weeks measuring pain and sleep scores during each phase of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have history of prior surgery and documented adhesions during laparoscopy or open laparotomy within 5 years * Must have undergone an evaluation to exclude other causes of abdominal pain * Abdominal pain must be present for greater than three months duration
Exclusion criteria
* Patients that are pregnant or breast feeding * Prior treatment with gabapentin, pregabalin or demonstrated sensitivity to these drugs * Patients who are immunocompromised * Patients with significant hepatic or renal insufficiency, or any significant hematologic disorder * History of illicit alcohol or drug abuse within one year * Documented serious or unstable medical or psychological condition * Malignancy within the past 5 years other than in situ squamous cell carcinoma of the skin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | Baseline and week 2 through week 12 | Patients were randomized to pregabalin or placebo 75 mg twice a day. Patients were allowed to double the dose on day 3 if adequate pain relief was not obtained. Abdominal pain reduction was measured on a Likert scale. A Likert scale assumes the intensity of pain is linear on a continuum from no pain at level 0 to severe pain at level 10. Patients were required to complete a daily dairy recording pain using the Likert 11-point numeric scale. The primary end point was a positive change in the daily pain diary of 2 points from each patient's baseline at weeks 8 after the completion of the blinded study and at week 12 during the open label portion of the study. After 7 weeks all patients are randomized to study drug pregabalin 150 to 300 mg daily for 4 additional weeks after a one week wash out with no medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improved Sleep Scores | Baseline and week 2 through week 12 | Absolute Improvement in Sleep by assessing Mean Daily sleep interference scores as measured weekly starting at baseline and reported weekly through week 12 excluding the first week. This score is an 11 point scale the documents the pain interference in sleep in the preceding 24 hours. 0 is no interference and 10 is pain completely disrupted sleep in the previous 24 hours. During the study patients recorded a daily sleep interference score based on 11 point scale (0-10) with the higher number being the most sleep interference |
Countries
United States
Participant flow
Recruitment details
Study was performed between December 2005 and August 2008. Patients were referred to the gastroenterology clinic if they had documented adhesions in the last 5 years, negative pain evaluation and pain that was thought to be from adhesions.
Pre-assignment details
After signing consent patients completed a one week baseline pain and sleep evaluation. Patients completed a Short-Form McGill Pain Questionaire during screening and at randomization. Patients had an average daily diary score of at least 4 on the the Likert scale during the baseline week and 5 diary recordings with stable pain medication doses.
Participants by arm
| Arm | Count |
|---|---|
| Active Drug 75-150 mg of pregabalin po BID
Pregabalin : First 7 weeks 75 or 150 mg of pregabalin po BID. Start at 75 mg and increase to 150 mg po BID if no improvement after 3 days | 11 |
| Placebo Placebo 75 or 150 mg po BID
Pregabalin : 75 mg po BID
Pregabalin : First 7 weeks 75 or 150 mg of pregabalin po BID. Start at 75 mg and increase to 150 mg po BID if no improvement after 3 days | 7 |
| Total | 18 |
Baseline characteristics
| Characteristic | Placebo | Active Drug | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 11 Participants | 16 Participants |
| Age, Continuous | 48.85 years STANDARD_DEVIATION 16.94 | 44.27 years STANDARD_DEVIATION 11.73 | 46.05 years STANDARD_DEVIATION 13.69 |
| Region of Enrollment United States | 7 participants | 11 participants | 18 participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 18 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 0 / 7 | 0 / 5 |
| other Total, other adverse events | 3 / 5 | 3 / 6 | 2 / 7 | 1 / 5 |
| serious Total, serious adverse events | 0 / 5 | 1 / 6 | 0 / 7 | 0 / 5 |
Outcome results
Primary
Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo
Patients were randomized to pregabalin or placebo 75 mg twice a day. Patients were allowed to double the dose on day 3 if adequate pain relief was not obtained. Abdominal pain reduction was measured on a Likert scale. A Likert scale assumes the intensity of pain is linear on a continuum from no pain at level 0 to severe pain at level 10. Patients were required to complete a daily dairy recording pain using the Likert 11-point numeric scale. The primary end point was a positive change in the daily pain diary of 2 points from each patient's baseline at weeks 8 after the completion of the blinded study and at week 12 during the open label portion of the study. After 7 weeks all patients are randomized to study drug pregabalin 150 to 300 mg daily for 4 additional weeks after a one week wash out with no medication.
Time frame: Baseline and week 2 through week 12
Population: The number of patients required per treatment group to achieve greater tha 80% power with alpha=0.05 were based on rates from published articles. The study was terminated early due to low enrollment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 11 open label | 2.23 units on a scale | Standard Deviation 1.55 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 4 | 4.84 units on a scale | Standard Deviation 1.28 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | baseline pain score | 5.8 units on a scale | Standard Deviation 0.96 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 5 | 4.32 units on a scale | Standard Deviation 1.57 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 10 open label | 2.27 units on a scale | Standard Deviation 0.74 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 6 | 3.88 units on a scale | Standard Deviation 1.82 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 2 | 5.22 units on a scale | Standard Deviation 2.29 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 7 | 3.92 units on a scale | Standard Deviation 1.76 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 12 open label | 1.13 units on a scale | Standard Deviation 1.15 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 8 open label with no study medication | 4.13 units on a scale | Standard Deviation 0.51 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 3 | 4.64 units on a scale | Standard Deviation 1.66 |
| Patients Treated With Placebo | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 9 open label | 2.21 units on a scale | Standard Deviation 0.74 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 3 | 1.88 units on a scale | Standard Deviation 1 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 10 open label | 1.84 units on a scale | Standard Deviation 2.13 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 11 open label | 1.46 units on a scale | Standard Deviation 2.03 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 12 open label | 1.68 units on a scale | Standard Deviation 1.93 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | baseline pain score | 6.15 units on a scale | Standard Deviation 0.72 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 2 | 2.87 units on a scale | Standard Deviation 2.28 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 9 open label | 2.06 units on a scale | Standard Deviation 2.24 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 4 | 3.31 units on a scale | Standard Deviation 2.6 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 5 | 2.72 units on a scale | Standard Deviation 2.05 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 6 | 2.49 units on a scale | Standard Deviation 1.7 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 7 | 2.53 units on a scale | Standard Deviation 2.19 |
| Patients Treated With Pregabalin | Absolute Adhesional Abdominal Pain Score Assessed at Baseline Through Week 12 in Patients Treated With Pregabalin 150-300 mg Daily Compared With Patients Given Look Alike Placebo | week 8 open label with no study medication | 2.46 units on a scale | Standard Deviation 2.36 |
Comparison: The number of patients required per treatment group to achieve a \>80% power with an alpha=0.05 were based on exact rates from reference articles cited in the paper. Patients were randomly assigned to active drug (pregabalin) or look alike placebo.p-value: <0.0595% CI: [0, 4]ANOVA
Secondary
Improved Sleep Scores
Absolute Improvement in Sleep by assessing Mean Daily sleep interference scores as measured weekly starting at baseline and reported weekly through week 12 excluding the first week. This score is an 11 point scale the documents the pain interference in sleep in the preceding 24 hours. 0 is no interference and 10 is pain completely disrupted sleep in the previous 24 hours. During the study patients recorded a daily sleep interference score based on 11 point scale (0-10) with the higher number being the most sleep interference
Time frame: Baseline and week 2 through week 12
Population: Pregabalin patients received 150mg or 300 mg for seven weeks and placebo patients received a look alike placebo for seven weeks. All patients received open label 300 mg of placebo for 4 weeks after a one week wash out phase at week 8.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients Treated With Placebo | Improved Sleep Scores | baseline | 4.66 units on a scale | Standard Deviation 2.79 |
| Patients Treated With Placebo | Improved Sleep Scores | week 2 | 3.4 units on a scale | Standard Deviation 3.41 |
| Patients Treated With Placebo | Improved Sleep Scores | week 3 | 3.26 units on a scale | Standard Deviation 3.11 |
| Patients Treated With Placebo | Improved Sleep Scores | week 4 | 3.54 units on a scale | Standard Deviation 2.81 |
| Patients Treated With Placebo | Improved Sleep Scores | week 5 | 3.06 units on a scale | Standard Deviation 2.9 |
| Patients Treated With Placebo | Improved Sleep Scores | week 6 | 2.74 units on a scale | Standard Deviation 2.6 |
| Patients Treated With Placebo | Improved Sleep Scores | week 7 | 3.18 units on a scale | Standard Deviation 2.27 |
| Patients Treated With Placebo | Improved Sleep Scores | week 8 open label no study medication | 3.30 units on a scale | Standard Deviation 1.13 |
| Patients Treated With Placebo | Improved Sleep Scores | week 9 open label | 1.70 units on a scale | Standard Deviation 0.88 |
| Patients Treated With Placebo | Improved Sleep Scores | week 10 open label | 1.25 units on a scale | Standard Deviation 0.98 |
| Patients Treated With Placebo | Improved Sleep Scores | week 11 open label | 1.18 units on a scale | Standard Deviation 0.95 |
| Patients Treated With Placebo | Improved Sleep Scores | week 12 open label | 0.56 units on a scale | Standard Deviation 0.55 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 11 open label | 1.39 units on a scale | Standard Deviation 2.04 |
| Patients Treated With Pregabalin | Improved Sleep Scores | baseline | 3.94 units on a scale | Standard Deviation 2.22 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 7 | 1.6 units on a scale | Standard Deviation 2.09 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 2 | 2.20 units on a scale | Standard Deviation 2.36 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 10 open label | 1.37 units on a scale | Standard Deviation 1.83 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 3 | 1.60 units on a scale | Standard Deviation 1.72 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 8 open label no study medication | 1.82 units on a scale | Standard Deviation 2.15 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 4 | 1.68 units on a scale | Standard Deviation 1.78 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 12 open label | 1.01 units on a scale | Standard Deviation 1.43 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 5 | 1.68 units on a scale | Standard Deviation 1.75 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 9 open label | 1.31 units on a scale | Standard Deviation 1.84 |
| Patients Treated With Pregabalin | Improved Sleep Scores | week 6 | 1.55 units on a scale | Standard Deviation 1.77 |
Comparison: The number of patients required per treatment group to achieve a \>80% power with an alpha=0.05 were based on the exact rates from the reference articles cited in the paper.p-value: <0.0595% CI: [0, 4]ANOVA