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Office hysteroscopic-guided pertubal bupivacaine (0.25%) infusion for endometriosis-associated pelvic pain: a randomized pilot study
Last registered on December 10, 2014

Pre-Trial

Trial Information
General Information
Title
Office hysteroscopic-guided pertubal bupivacaine (0.25%) infusion for endometriosis-associated pelvic pain: a randomized pilot study
RCT ID
AEARCTR-0000573
Initial registration date
December 10, 2014
Last updated
December 10, 2014 4:20 PM EST
Location(s)
Region
Primary Investigator
Affiliation
Other Primary Investigator(s)
Additional Trial Information
Status
Completed
Start date
2010-06-09
End date
2013-07-30
Secondary IDs
Abstract
Objectives: To test for the feasibility and short-term effectiveness of the office
hysteroscopic-guided pertubal bupivacaine infusion (0.25%) for treating endometriosisassociated
pelvic pain.
Methods: In a randomized double-blind placebo-controlled pilot trial, 76 women with
pelvic endometriosis suffering from chronic pelvic pain (CPP) for more than 6 months
and defined as a pain score > VAS 50mm (visual analogue score) were enrolled.
Eligible patients had laparoscopically confirmed pelvic endometriosis (stage I-IV) and
patent fallopian tubes. Sixty CPP patients were randomly assigned to receive either
hysteroscopic-guided pertubal diluted bupivacaine (0.25%) infusion at a single
preovulatory outpatient setting (group I, n=30) or placebo (group II, n=30). Pelvic pain
scores, visual analogue scores and monthly visual rating scales (VRSmonthly) were
assessed at baseline and at 1, 2, and 3 months after joining the protocol. At the end of
the study, women completed a questionnaire designed to evaluate the overall patient
satisfaction rate about the procedure
Results: All patients were available for analysis. After identification, the baseline clinical
characteristics for both groups were comparable. There were statistically significant
improvements from corresponding baseline scores at 1, 2, and 3 months for the VAS,
the VRSmonthly, and the pelvic pain scores in the bupivacaine treated group
compared with placebo (P<.05). Along the 3-months duration of the study, all domains
were demonstrated to be substantially lower than the baseline data. At the end of the
study, women in the bupivacaine group expressed a higher degree of patient
satisfaction that was independent of age, duration or severity of the symptoms (73% vs
7%; P<.05). The procedure was well-tolerated by all patients without any adverse
effects.
Conclusions: Office pertubal hysteroscopic-guided bupivacaine (0.25%) infusion has a
place in the management of women with endometriosis-associated pelvic pain. It offers
a minimally invasive and more cost-effective alternative to current treatments for at
least 3 months.
External Link(s)
Registration Citation
Citation
Shokeir, Tarek. 2014. "Office hysteroscopic-guided pertubal bupivacaine (0.25%) infusion for endometriosis-associated pelvic pain: a randomized pilot study." AEA RCT Registry. December 10. https://doi.org/10.1257/rct.573-1.0.
Former Citation
Shokeir, Tarek. 2014. "Office hysteroscopic-guided pertubal bupivacaine (0.25%) infusion for endometriosis-associated pelvic pain: a randomized pilot study." AEA RCT Registry. December 10. https://www.socialscienceregistry.org/trials/573/history/3214.
Experimental Details
Interventions
Intervention(s)
Patient population:
This randomized, placebo-controlled, double-blind pilot study was conducted between June 2010 and July 2013. The protocol was approved by local ethics committee of the institution. Each subject signed an informed consent to participate in this trial.
During this period, 76 women complaining of chronic pelvic pain (CPP) for > 6 months and defined as a pain score > VAS 50mm (visual analogue scale) were enrolled. Eligible patients had laparoscopically confirmed pelvic endometriosis (stage I-IV) and patent fallopian tubes. The exclusion criteria were age <18 years, any hormonal therapy in preceding 3 months, a desire to conceive within 1 year, or occluded fallopian tubes with or without pelvic adhesions. Cases with proved non-gynecologic causes of CPP (intestinal, urinary, and/or musculoskletal) were also excluded from the study. Each patient was advised to stop any analgesic medications before enrollment into the study. Patients with a known hypersensitivity or any contraindications to bupivacaine or to any local anesthetic agent of the amide-type were also excluded from the study.
All women in this trial underwent complete pelvic examination and high-resolution transvaginal ultrasonography. Basic work-up investigations to exclude concomitant non-gynecologic causes of CPP including mid-stream urine analysis, stool analysis, intravenous urogram, and full blood count whenever indicated were done. Only subjects with purely diagnosed pelvic endometriosis and patent fallopian tubes were included in this study.
Randomization:
At the time of office recruitment, patients were randomized in a ratio of 1:1 that was performed in accordance with a computer-generated randomization sequence using numbered, sealed envelopes to have either pertubal hysteroscopic-guided diluted bupivacaine (0.25%) infusion [Single-dose vial 10 ml + 100 ml Ringer solution] (group I, n=30) or placebo infusion [100 ml Ringer solution alone] (group II, n=30). All patients and experimenters (while delivering treatment, scanning and analyzing data) were blinded to the type of treatment.
The allocated study solution was provided to the surgeon intraoperatively by senior nursing staff. Solutions were indistinguishable and were preloaded into identical unlabeled Ringer solution bottles.
Pertubal infusion method:
The procedure was carried-out in a day-case endoscopic suite. One treatment setting was to be given preovulatory on cycle Day 7-12. Under paracervical block, and using Ringer solution as a uterine distending medium (Hysteromat, Karl Storz, Germany), an office hysteroscope (2.7 mm, Karl Storz, Tuttlingen, Germany) was passed and one tubal orifice was identified. Under a hysteroscopic guidance, a 3-Fr ureteric catheter was introduced, cannulated through the tubal ostium and passed proximally for 2-3 cm. After successful cannulation, diluted bupivacaine (0.25%, 10 ml with Ringer solution 100 ml) [Marcaine, AstraZenica, Istanbul, Turkey] was then infused through the catheter over a 15-20 min period. None of the patients used any adjunctive measures or analgesics following the original treatment.
Follow-up:
Follow-up visits after hysteroscopic pertubal infusion were scheduled after 1, 2, and 3 months. A month before each visit, the patients completed a diary of their pain score. These were collected at the follow-up visit and new diaries given for the next visit. Grading of symptoms and physical findings were assessed at each clinic visit. The duration of treatment was completed in 3 months. Each patient was advised to stop any analgesic medications and to use barrier contraception throughout the study.
Outcome measures:
For the month preceding the trial, each patient completed a diary for generation of baseline variables, which were used for the assessment of the response to treatment. Response to treatment was assessed subjectively by changes in the variables, which included the patient's perception of pelvic pain severity using a visual analogue scale (VAS), her rating of both types of pelvic pain (dysmenorrheal and/or non-cycling pain) on a daily verbal rating scale (VRS), and a monthly verbal pelvic pain score (VRSmonthly). Satisfaction rates were also assessed.
Measurement tool:
The VAS was a subjective assessment of the pain on a scale of 0 (no pain) to 10 (most severe pain). It was recorded on a 10cm ruler in the diary at each follow-up visit and reflected the severity of this symptom as perceived by the patient in the preceding month (daily VAS). A monthly score (VRSmonthly) was then generated from the summation of daily VAS over a 28-day period (0, no pain; 100, maximum pain) at 1, 2, and 3 months.
On a multiple-choice questionnaire, an overall patient satisfaction rate that was independent of age, duration or severity of the symptoms was used to assess performance and satisfaction (satisfied, uncertain, dissatisfied) in daily activities at the end of the study taking into account the undesirable side effects.
Sample size justification:
Sample size was calculated using Epi Info® version 6.0, setting the type- I error (α) at 0.05 and the power (1- β) at 0.8, data from previous studies (5-7). According to these values and at 95% confidence interval, a minimal sample size of 60 patients was accepted to reach statistically accepted figure. Therefore, a total number of 76 patients were recruited in this study.
Data collection and statistical analysis:
Data concerning subjects who had undergone the office procedure since June 2010 were collected prospectively. The case notes of those with minimum of 3-months follow-up were further reviewed for the purposes of this report.
Epi Info® version 6.0 was used to record and statistically analyse the data. Values at the time of the hysteroscopic-guided pertubal bupivacaine infusion (i.e time 0) were compared with those at three time points (1, 2 and 3 months) after infusion using the paired t test, Mann-Whitney U test, Wilcoson and Friedman two-way ANOVA tests as appropriate. A level of significance of P<.05 was accepted for the study.
Intervention Start Date
2010-06-15
Intervention End Date
2013-07-30
Primary Outcomes
Primary Outcomes (end points)
For the month preceding the trial, each patient completed a diary for generation of baseline variables, which were used for the assessment of the response to treatment. Response to treatment was assessed subjectively by changes in the variables, which included the patient's perception of pelvic pain severity using a visual analogue scale (VAS), her rating of both types of pelvic pain (dysmenorrheal and/or non-cycling pain) on a daily verbal rating scale (VRS), and a monthly verbal pelvic pain score (VRSmonthly). Satisfaction rates were also assessed.
Measurement tool:
The VAS was a subjective assessment of the pain on a scale of 0 (no pain) to 10 (most severe pain). It was recorded on a 10cm ruler in the diary at each follow-up visit and reflected the severity of this symptom as perceived by the patient in the preceding month (daily VAS). A monthly score (VRSmonthly) was then generated from the summation of daily VAS over a 28-day period (0, no pain; 100, maximum pain) at 1, 2, and 3 months.
On a multiple-choice questionnaire, an overall patient satisfaction rate that was independent of age, duration or severity of the symptoms was used to assess performance and satisfaction (satisfied, uncertain, dissatisfied) in daily activities at the end of the study taking into account the undesirable side effects.
Primary Outcomes (explanation)
Secondary Outcomes
Secondary Outcomes (end points)
Secondary Outcomes (explanation)
Experimental Design
Experimental Design
Patient population:
This randomized, placebo-controlled, double-blind pilot study was conducted between June 2010 and July 2013. The protocol was approved by local ethics committee of the institution. Each subject signed an informed consent to participate in this trial.
During this period, 76 women complaining of chronic pelvic pain (CPP) for > 6 months and defined as a pain score > VAS 50mm (visual analogue scale) were enrolled. Eligible patients had laparoscopically confirmed pelvic endometriosis (stage I-IV) and patent fallopian tubes. The exclusion criteria were age <18 years, any hormonal therapy in preceding 3 months, a desire to conceive within 1 year, or occluded fallopian tubes with or without pelvic adhesions. Cases with proved non-gynecologic causes of CPP (intestinal, urinary, and/or musculoskletal) were also excluded from the study. Each patient was advised to stop any analgesic medications before enrollment into the study. Patients with a known hypersensitivity or any contraindications to bupivacaine or to any local anesthetic agent of the amide-type were also excluded from the study.
All women in this trial underwent complete pelvic examination and high-resolution transvaginal ultrasonography. Basic work-up investigations to exclude concomitant non-gynecologic causes of CPP including mid-stream urine analysis, stool analysis, intravenous urogram, and full blood count whenever indicated were done. Only subjects with purely diagnosed pelvic endometriosis and patent fallopian tubes were included in this study.
Randomization:
At the time of office recruitment, patients were randomized in a ratio of 1:1 that was performed in accordance with a computer-generated randomization sequence using numbered, sealed envelopes to have either pertubal hysteroscopic-guided diluted bupivacaine (0.25%) infusion [Single-dose vial 10 ml + 100 ml Ringer solution] (group I, n=30) or placebo infusion [100 ml Ringer solution alone] (group II, n=30). All patients and experimenters (while delivering treatment, scanning and analyzing data) were blinded to the type of treatment.
The allocated study solution was provided to the surgeon intraoperatively by senior nursing staff. Solutions were indistinguishable and were preloaded into identical unlabeled Ringer solution bottles.
Pertubal infusion method:
The procedure was carried-out in a day-case endoscopic suite. One treatment setting was to be given preovulatory on cycle Day 7-12. Under paracervical block, and using Ringer solution as a uterine distending medium (Hysteromat, Karl Storz, Germany), an office hysteroscope (2.7 mm, Karl Storz, Tuttlingen, Germany) was passed and one tubal orifice was identified. Under a hysteroscopic guidance, a 3-Fr ureteric catheter was introduced, cannulated through the tubal ostium and passed proximally for 2-3 cm. After successful cannulation, diluted bupivacaine (0.25%, 10 ml with Ringer solution 100 ml) [Marcaine, AstraZenica, Istanbul, Turkey] was then infused through the catheter over a 15-20 min period. None of the patients used any adjunctive measures or analgesics following the original treatment.
Follow-up:
Follow-up visits after hysteroscopic pertubal infusion were scheduled after 1, 2, and 3 months. A month before each visit, the patients completed a diary of their pain score. These were collected at the follow-up visit and new diaries given for the next visit. Grading of symptoms and physical findings were assessed at each clinic visit. The duration of treatment was completed in 3 months. Each patient was advised to stop any analgesic medications and to use barrier contraception throughout the study.
Experimental Design Details
Randomization Method
Randomization:
At the time of office recruitment, patients were randomized in a ratio of 1:1 that was performed in accordance with a computer-generated randomization sequence using numbered, sealed envelopes to have either pertubal hysteroscopic-guided diluted bupivacaine (0.25%) infusion [Single-dose vial 10 ml + 100 ml Ringer solution] (group I, n=30) or placebo infusion [100 ml Ringer solution alone] (group II, n=30). All patients and experimenters (while delivering treatment, scanning and analyzing data) were blinded to the type of treatment.
The allocated study solution was provided to the surgeon intraoperatively by senior nursing staff. Solutions were indistinguishable and were preloaded into identical unlabeled Ringer solution bottles.
Randomization Unit
At the time of office recruitment, patients were randomized in a ratio of 1:1 that was performed in accordance with a computer-generated randomization sequence using numbered, sealed envelopes to have either pertubal hysteroscopic-guided diluted bupivacaine (0.25%) infusion [Single-dose vial 10 ml + 100 ml Ringer solution] (group I, n=30) or placebo infusion [100 ml Ringer solution alone] (group II, n=30). All patients and experimenters (while delivering treatment, scanning and analyzing data) were blinded to the type of treatment.

The allocated study solution was provided to the surgeon intraoperatively by senior nursing staff. Solutions were indistinguishable and were preloaded into identical unlabeled Ringer solution bottles.
Was the treatment clustered?
Yes
Experiment Characteristics
Sample size: planned number of clusters
At the time of office recruitment, patients were randomized in a ratio of 1:1 that was performed in accordance with a computer-generated randomization sequence using numbered, sealed envelopes to have either pertubal hysteroscopic-guided diluted bupivacaine (0.25%) infusion [Single-dose vial 10 ml + 100 ml Ringer solution] (group I, n=30) or placebo infusion [100 ml Ringer solution alone] (group II, n=30). All patients and experimenters (while delivering treatment, scanning and analyzing data) were blinded to the type of treatment.
Sample size: planned number of observations
76 patients.
Sample size (or number of clusters) by treatment arms
50 patients for each group.
Minimum detectable effect size for main outcomes (accounting for sample design and clustering)
Sample size was calculated using Epi Info® version 6.0, setting the type- I error (α) at 0.05 and the power (1- β) at 0.8, data from previous studies (5-7). According to these values and at 95% confidence interval, a minimal sample size of 60 patients was accepted to reach statistically accepted figure. Therefore, a total number of 76 patients were recruited in this study.
IRB
INSTITUTIONAL REVIEW BOARDS (IRBs)
IRB Name
Mansoura University Research Committee
IRB Approval Date
2010-05-31
IRB Approval Number
433
Post-Trial
Post Trial Information
Study Withdrawal
Intervention
Is the intervention completed?
No
Is data collection complete?
Data Publication
Data Publication
Is public data available?
No
Program Files
Program Files
Reports and Papers
Preliminary Reports
Relevant Papers