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Effect of Anti TNFa Upon Deep Endometriosis Associated Pain (Infliximab)

Primary Purpose

Endometriosis

Status

Completed

Phase

Phase 2

Locations

Belgium

Study Type

Interventional

Intervention

anti TNFa monoclonal antibody - Infliximab

placebo

About this trial

This is an interventional treatment trial for Endometriosis focused on measuring deep endometriosis, pelvic pain, infliximab, anti TNFa

Eligibility Criteria

20 Years - 45 Years (Adult)FemaleDoes not accept 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.

Sites / Locations

University Hospital Gasthuisberg

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

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)

Outcomes

Primary Outcome Measures

Endometriosis associated pain

Secondary Outcome Measures

decrease in volume of deep endometriosis nodule

Full Information

NCT ID

NCT00604864

First Posted

January 17, 2008

Last Updated

January 29, 2008

Sponsor

KU Leuven

1. Study Identification

Unique Protocol Identification Number

NCT00604864

Brief Title

Effect of Anti TNFa Upon Deep Endometriosis Associated Pain

Acronym

Infliximab

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2008

Overall Recruitment Status

Completed

Study Start Date

February 2004 (undefined)

Primary Completion Date

February 2005 (Actual)

Study Completion Date

November 2005 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

KU Leuven

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Endometriosis

Keywords

deep endometriosis, pelvic pain, infliximab, anti TNFa

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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)

Arm Title

Arm Type

Placebo Comparator

Arm Description

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)

Intervention Type

Drug

Intervention Name(s)

anti TNFa monoclonal antibody - Infliximab

Intervention Description

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

Intervention Name(s)

placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Endometriosis associated pain

Time Frame

By the clinician after 1, 2 and 3 months ; by the patient daily for 3 months

Secondary Outcome Measure Information:

Title

decrease in volume of deep endometriosis nodule

Time Frame

after 1, 2 and 3 months of treatment

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Philippe R Koninckx, MD, PhD

Organizational Affiliation

Catholic University Leuven

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Gasthuisberg

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

12. IPD Sharing Statement

Citations:

PubMed Identifier

10920097

Citation

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.

Results Reference

background

PubMed Identifier

15128354

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. doi: 10.1111/j.1572-0241.2004.04148.x.

Results Reference

background

PubMed Identifier

11011074

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. doi: 10.1016/s0165-0378(00)00073-5.

Results Reference

background

PubMed Identifier

18556683

Citation

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.

Results Reference

derived

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Effect of Anti TNFa Upon Deep Endometriosis Associated Pain

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