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Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial

Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial
Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial
Background
Chronic pelvic pain affects 2–24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology.

Methods
We performed a multicentre, randomised, double-blind, placebo-controlled randomised trial in 39 UK hospital centres. Eligible participants were women with chronic pelvic pain (with or without dysmenorrhoea or dyspareunia) of at least 3 months duration. Inclusion criteria were 18–50 years of age, use or willingness to use contraception to avoid pregnancy, and no obvious pelvic pathology at laparoscopy, which must have taken place at least 2 weeks before consent but less than 36 months previously. Participants were randomly assigned in a 1:1 ratio to receive gabapentin (titrated to a maximum dose of 2700 mg daily) or matching placebo for 16 weeks. The online randomisation system minimised allocations by presence or absence of dysmenorrhoea, psychological distress, current use of hormonal contraceptives, and hospital centre. The appearance, route, and administration of the assigned intervention were identical in both groups. Patients, clinicians, and research staff were unaware of the trial group assignments throughout the trial. Participants were unmasked once they had provided all outcome data at week 16–17, or sooner if a serious adverse event requiring knowledge of the study drug occurred. The dual primary outcome measures were worst and average pain scores assessed separately on a numerical rating scale in weeks 13–16 after randomisation, in the intention-to-treat population. Self-reported adverse events were assessed according to intention-to-treat principles. This trial is registered with the ISRCTN registry, ISCRTN77451762.

Findings
Participants were screened between Nov 30, 2015, and March 6, 2019, and 306 were randomly assigned (153 to gabapentin and 153 to placebo). There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13–16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was −1·4 (SD 2·3) in the gabapentin group and −1·2 (SD 2·1) in the placebo group (adjusted mean difference −0·20 [97·5% CI −0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was −1·1 (SD 2·0) in the gabapentin group and −0·9 (SD 1·8) in the placebo group (adjusted mean difference −0·18 [97·5% CI −0·71 to 0·35]; p=0·45). More women had a serious adverse event in the gabapentin group than in the placebo group (10 [7%] of 153 in the gabapentin group compared with 3 [2%] of 153 in the placebo group; p=0·04). Dizziness, drowsiness, and visual disturbances were more common in the gabapentin group.

Interpretation
This study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology.

Funding
National Institute for Health Research.
0140-6736
909-917
Horne, Andrew W.
82f2bcc1-6e8d-454c-83d2-744e6c9bd831
Vincent, Katy
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Hewitt, Catherine A.
a3cf451c-8179-41c2-bcf3-ff8dfc840bab
Middleton, Lee J.
5fb39a8c-1d0e-4aaf-b93d-077900d7b56d
Koscielniak, Magda
0f7f8902-8467-48c9-8653-4afb13024d21
Szubert, Wojciech
f675e41e-278b-42c0-a8c3-d16dac36746c
Doust, Ann M.
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Daniels, Jane P.
2f3a7a69-7c19-47e8-b1a7-ebdd74e313d9
Cheong, Ying
4efbba2a-3036-4dce-82f1-8b4017952c83
on behalf of the GaPP2 collaborative
Horne, Andrew W.
82f2bcc1-6e8d-454c-83d2-744e6c9bd831
Vincent, Katy
6e4a96d4-fddd-42a4-8ff5-14bb30671184
Hewitt, Catherine A.
a3cf451c-8179-41c2-bcf3-ff8dfc840bab
Middleton, Lee J.
5fb39a8c-1d0e-4aaf-b93d-077900d7b56d
Koscielniak, Magda
0f7f8902-8467-48c9-8653-4afb13024d21
Szubert, Wojciech
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Doust, Ann M.
82c883dd-7531-47c7-86c7-af2605d912a5
Daniels, Jane P.
2f3a7a69-7c19-47e8-b1a7-ebdd74e313d9
Cheong, Ying
4efbba2a-3036-4dce-82f1-8b4017952c83

Horne, Andrew W., Vincent, Katy, Hewitt, Catherine A., Middleton, Lee J., Koscielniak, Magda, Szubert, Wojciech, Doust, Ann M. and Daniels, Jane P. , on behalf of the GaPP2 collaborative (2020) Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet, 396 (10255), 909-917. (doi:10.1016/S0140-6736(20)31693-7).

Record type: Article

Abstract

Background
Chronic pelvic pain affects 2–24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology.

Methods
We performed a multicentre, randomised, double-blind, placebo-controlled randomised trial in 39 UK hospital centres. Eligible participants were women with chronic pelvic pain (with or without dysmenorrhoea or dyspareunia) of at least 3 months duration. Inclusion criteria were 18–50 years of age, use or willingness to use contraception to avoid pregnancy, and no obvious pelvic pathology at laparoscopy, which must have taken place at least 2 weeks before consent but less than 36 months previously. Participants were randomly assigned in a 1:1 ratio to receive gabapentin (titrated to a maximum dose of 2700 mg daily) or matching placebo for 16 weeks. The online randomisation system minimised allocations by presence or absence of dysmenorrhoea, psychological distress, current use of hormonal contraceptives, and hospital centre. The appearance, route, and administration of the assigned intervention were identical in both groups. Patients, clinicians, and research staff were unaware of the trial group assignments throughout the trial. Participants were unmasked once they had provided all outcome data at week 16–17, or sooner if a serious adverse event requiring knowledge of the study drug occurred. The dual primary outcome measures were worst and average pain scores assessed separately on a numerical rating scale in weeks 13–16 after randomisation, in the intention-to-treat population. Self-reported adverse events were assessed according to intention-to-treat principles. This trial is registered with the ISRCTN registry, ISCRTN77451762.

Findings
Participants were screened between Nov 30, 2015, and March 6, 2019, and 306 were randomly assigned (153 to gabapentin and 153 to placebo). There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13–16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was −1·4 (SD 2·3) in the gabapentin group and −1·2 (SD 2·1) in the placebo group (adjusted mean difference −0·20 [97·5% CI −0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was −1·1 (SD 2·0) in the gabapentin group and −0·9 (SD 1·8) in the placebo group (adjusted mean difference −0·18 [97·5% CI −0·71 to 0·35]; p=0·45). More women had a serious adverse event in the gabapentin group than in the placebo group (10 [7%] of 153 in the gabapentin group compared with 3 [2%] of 153 in the placebo group; p=0·04). Dizziness, drowsiness, and visual disturbances were more common in the gabapentin group.

Interpretation
This study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology.

Funding
National Institute for Health Research.

Text
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More information

Accepted/In Press date: 1 January 2020
e-pub ahead of print date: 24 September 2020
Published date: 26 September 2020

Identifiers

Local EPrints ID: 444244
URI: http://eprints.soton.ac.uk/id/eprint/444244
ISSN: 0140-6736
PURE UUID: dfa0ed10-8202-44ec-b92d-1a4095c5725a
ORCID for Ying Cheong: ORCID iD orcid.org/0000-0001-7687-4597

Catalogue record

Date deposited: 02 Oct 2020 16:37
Last modified: 10 Jun 2022 01:39

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Contributors

Author: Andrew W. Horne
Author: Katy Vincent
Author: Catherine A. Hewitt
Author: Lee J. Middleton
Author: Magda Koscielniak
Author: Wojciech Szubert
Author: Ann M. Doust
Author: Jane P. Daniels
Author: Ying Cheong ORCID iD
Corporate Author: on behalf of the GaPP2 collaborative

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