Infliximab: Effect of Anti TNFa Upon Deep Endometriosis Associated Pain

Sponsor

KU Leuven (Other)

Overall Status

Completed

CT.gov ID

NCT00604864

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Deep endometriosis associated pain is believed to be caused by inflammation. Anti TNFa has been proved to be an effective treatment for other inflammation related conditions as Crohn's disease Endometriosis is associated with an inflammatory response in the pelvis, which is mediated by a number of cytokines including TNF-α. It has therefore been suggested that infliximab, an anti-TNF-α monoclonal antibody, might relieve pain in affected women.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis	Drug: anti TNFa monoclonal antibody - Infliximab Drug: placebo	Phase 2

Detailed Description

In this pilot study, 21 women with severe endometriosis-associated pain and a rectovaginal nodule, at least 1 cm in diameter on clinical examination, were randomised in a 2 to 1 ratio to receive intravenous infliximab (n=14) or placebo (n=7) in the three months prior to laparoscopic laser excision of the nodule.

After a 1 month observation period, all women received three infusions of infliximab (5mg/kg) or placebo over the course of 6 weeks. Surgery was performed 3 months later and follow-up continued for a further 6 months. The primary endpoint was the total pain burden (dysmenorrhoea, deep dyspareunia and non-menstrual pain) rated on a daily basis by the patient using standard pain scales and analgesic intake as the outcome measures . Secondary endpoints included the volume of the endometriotic nodule assessed clinically and on transvaginal ultrasound, the amount of pelvic tenderness on clinical examination and the presence of other endometriotic lesions at laparoscopy.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Anti TNFa Treatment for Deep Endometriosis Associated Pain : a Randomised Placebo Controlled Trial.

Study Start Date :

Feb 1, 2004

Actual Primary Completion Date :

Feb 1, 2005

Actual Study Completion Date :

Nov 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 women with a deep endometriosis nodule of at least 1 cm in diameter; and severe pain (at least one severe pain score on Biberoglu Behrman scale)	Drug: anti TNFa monoclonal antibody - Infliximab Chimeric A2 (infliximab, RemicadeTM) IgG ; 100 mg infliximab IgG, Infliximab was freshly prepared immediately before each administration. Infliximab or placebo was administered as a slow infusion of 250mL on weeks 0, 2 and 6. Women were closely observed during, and for 1 hour after, the infusion in the event of any serious adverse reactions.
Placebo Comparator: 2 women with a deep endometriosis nodule of at least 1 cm in diameter; and severe pain (at least one severe pain score on Biberoglu Behrman scale)	Drug: placebo Placebo

Arm

Intervention/Treatment

Experimental: 1

women with a deep endometriosis nodule of at least 1 cm in diameter; and severe pain (at least one severe pain score on Biberoglu Behrman scale)

Drug: anti TNFa monoclonal antibody - Infliximab

Chimeric A2 (infliximab, RemicadeTM) IgG ; 100 mg infliximab IgG, Infliximab was freshly prepared immediately before each administration. Infliximab or placebo was administered as a slow infusion of 250mL on weeks 0, 2 and 6. Women were closely observed during, and for 1 hour after, the infusion in the event of any serious adverse reactions.

Placebo Comparator: 2

women with a deep endometriosis nodule of at least 1 cm in diameter; and severe pain (at least one severe pain score on Biberoglu Behrman scale)

Drug: placebo

Placebo

Outcome Measures

Primary Outcome Measures

Endometriosis associated pain [By the clinician after 1, 2 and 3 months ; by the patient daily for 3 months]

Secondary Outcome Measures

decrease in volume of deep endometriosis nodule [after 1, 2 and 3 months of treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

The patients (aged 18-50 years) were all recruited from a single, tertiary referral hospital at Leuven University, Belgium, specialising in the surgical treatment of severe endometriosis.
All the women were symptomatic and scheduled for surgical excision of a rectovaginal nodule, at least 1 cm in diameter, diagnosed on the basis of clinical examination at the time of menstruation.
All the women had a menstrual cycle occurring every 25 to 40 days.
If previously treated with hormonal medication for endometriosis, at least 3 months must have elapsed and they must have had at least two menstrual cycles since stopping treatment.
Unless the women had previously been sterilised, they had to agree to use a double-barrier method of contraception for the duration of the study and for up to 6 months after receiving the last infusion.
The study was approved by the Institutional Review Board of Leuven University.
Written, informed consent was obtained before any study related procedures were performed.

Exclusion Criteria:

Evidence on chest x-ray in the previous 3 months of old or currently active TB, or other history/evidence of active TB, even if adequately treated
Evidence of serious infections (such as pneumonia or pyelonephritis) in the previous 3 months
Evidence of a documented HIV infection, active hepatitis-B or C, or an opportunistic infection (e.g. herpes zoster, cytomegalovirus, pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) in the previous 6 months
Previous transplant surgery, a lymphoproliferative disorder or other malignancy
Positive cervical cytology in the previous 6 months
Previous treatment with infliximab, any drug known to affect TNF-α levels, e.g. pentoxifylline, thalidomide and etanercept, or any human/murine recombinant products
Known allergy to murine products
Use of other investigational drugs within 1 month of recruitment or within 5 half-lives of the investigational agent, whichever was longer
Any haematological or biochemical abnormalities on routine screening.
Subjects were also excluded if there was any pelvic pathology on transvaginal ultrasound scan (TVS) other than small uterine fibroids (< 4 cm in diameter) and an ovarian endometrioma or endometriotic nodule.