Effect of Anti TNFa Upon Deep Endometriosis Associated Pain

NCT ID: NCT00604864

Last Updated: 2008-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2005-11-30

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.

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.

Conditions

Endometriosis

Keywords

deep endometriosis; pelvic pain; infliximab; anti TNFa

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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)

Group Type: EXPERIMENTAL

anti TNFa monoclonal antibody - Infliximab

Intervention Type: DRUG

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.

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)

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Placebo

Interventions

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.

Intervention Type: DRUG

placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

UZ Gasthuisberg, Catholic University Leuven

Principal Investigators

Philippe R Koninckx, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Catholic University Leuven

Locations

University Hospital Gasthuisberg

Leuven, , Belgium

Countries

Belgium

References

Anaf V, Simon P, El Nakadi I, Fayt I, Buxant F, Simonart T, Peny MO, Noel JC. Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Hum Reprod. 2000 Aug;15(8):1744-50. doi: 10.1093/humrep/15.8.1744.

Reference Type: BACKGROUND

PMID: 10920097 (View on PubMed)

Colombel JF, Loftus EV Jr, Tremaine WJ, Pemberton JH, Wolff BG, Young-Fadok T, Harmsen WS, Schleck CD, Sandborn WJ. Early postoperative complications are not increased in patients with Crohn's disease treated perioperatively with infliximab or immunosuppressive therapy. Am J Gastroenterol. 2004 May;99(5):878-83. doi: 10.1111/j.1572-0241.2004.04148.x.

Reference Type: BACKGROUND

PMID: 15128354 (View on PubMed)

D'Antonio M, Martelli F, Peano S, Papoian R, Borrelli F. Ability of recombinant human TNF binding protein-1 (r-hTBP-1) to inhibit the development of experimentally-induced endometriosis in rats. J Reprod Immunol. 2000 Oct-Nov;48(2):81-98. doi: 10.1016/s0165-0378(00)00073-5.

Reference Type: BACKGROUND

PMID: 11011074 (View on PubMed)

Koninckx PR, Craessaerts M, Timmerman D, Cornillie F, Kennedy S. Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod. 2008 Sep;23(9):2017-23. doi: 10.1093/humrep/den177. Epub 2008 Jun 12.

Reference Type: DERIVED

PMID: 18556683 (View on PubMed)

Other Identifiers

trial_EU-0053/endometriosis

Identifier Type: -

Identifier Source: org_study_id