Effect of Anti TNFa Upon Deep Endometriosis Associated Pain

Endometriosis Clinical Trial

— Infliximab  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00604864
• Other study ID #: trial_EU-0053/endometriosis
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2008
• Last updated: January 29, 2008
• Start date: February 2004
• Est. completion date: November 2005

Study information

• Verified date: January 2008
• Source: Katholieke Universiteit Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2005
• Est. primary completion date: February 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 45 Years

Eligibility

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-a 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometriosis

Intervention

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
Placebo

Locations

Country	Name	City	State
Belgium	University Hospital Gasthuisberg	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Katholieke Universiteit Leuven

Country where clinical trial is conducted

Belgium, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endometriosis associated pain		By the clinician after 1, 2 and 3 months ; by the patient daily for 3 months	No
Secondary	decrease in volume of deep endometriosis nodule		after 1, 2 and 3 months of treatment	No