The IPLA-OVCA Trial, Intra-Peritoneal Local Anaesthetics in Ovarian Cancer

NCT04065009 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 20190729
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Surgery and chemotherapy combined constitute first line treatment in women with advanced ovarian cancer. The aim of surgery apart from staging is cytoreduction, i.e. surgical resection of tumour. Radical resection of all tumour visible by the naked eye followed by adjuvant chemotherapy is associated with best chance of prolonged survival. However, because of tumour dissemination in the peritoneal cavity, radical surgery is often very extensive with surgery in all quadrants of the abdomen and multi-organ resection with substantial risk of postoperative severe complications and subsequent delay in administration of adjuvant chemotherapy. Longer time-interval between surgery to start of adjuvant chemotherapy has been associated with decrease in survival. Surgery presents opportunities not only for eradicating tumours but, paradoxically, also for proliferation and invasion of residual cancer cells. It increases the shedding of malignant cells into the blood and lymphatic circulations, inhibits their apoptosis and potentiates their invasion capacity. Additionally, the immune system, the inflammatory system and the neuroendocrine system react to surgery with important changes, which have been proven to promote progression of cancer. Several anaesthesia-related factors play an important role in perioperative tumorigenesis such as inhalational anaesthetics, opiate analgesics, local anaesthetics and regional anaesthesia, all of which may impact short-term morbidity and long-term mortality. A previous randomized placebo-controlled pilot study suggests that women who receive local anesthetics intraperitoneally preoperatively have a significantly decreased time-interval to initiation of adjuvant chemotherapy. In a prospective, randomised, multi-centre study, we plan to further assess if intraperitoneal local anaesthetics administered perioperatively during 72 h leads to early start of chemotherapy compared to placebo in patients undergoing cytoreductive surgery for FIGO stage III-IV ovarian cancer.

Conditions

Advanced Ovarian Cancer

Keywords

Local Anesthesia; Time-interval from surgery to adjuvant chemotherapy; advanced ovarian cancer

Outcome Measures

Primary Outcomes (1)

• Time-interval from upfront surgery to adjuvant chemotherapy

  Days from surgery to first infusion of adjuvant chemotherapy

  Number of days to start of adjuvant chemotherapy (0 - 60 days)

Secondary Outcomes (4)

• Postoperative complications

  30 days postoperatively

• Overall survival

  3 and 5 years after surgery

• Postoperative quality of recovery

  Perioperatively

• Postoperative morbidity

  Perioperatively

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Normal saline administered intraperitoneally at defined times during upfront surgery and intermittently postoperatively for 72 hours

Drug: Saline Solution

Experimental

EXPERIMENTAL

Local anesthetic (ropivacaine) administered intraperitoneally at defined times during upfront surgery and intermittently postoperatively for 72 hours

Drug: Ropivacaine

Interventions

Ropivacaine DRUG

Experimental drug will be administered intraperitoneally

Also known as: Narop

Experimental

Saline Solution DRUG

Placebo will be administered intraperitoneally

Also known as: Normal saline

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ASA I-III
• Scheduled for upfront cytoreductive surgery for presumed stage III or IV epithelial ovarian cancer
• Signed written informed consent

You may not qualify if:

• Contraindication to epidural anesthesia
• Allergy to any component drugs used during epidural or intraperitoneal anesthesia (Ropivacaine, Sufentanil)
• Uncontrolled renal, liver, heart failure or ischemic heart disease
• Speech, language or cognitive difficulties
• Women in whom cytoreductive surgery is not attempted at time of upfront laparotomy due to extent of disease

Sponsors & Collaborators

• Karolinska Institutet: lead
• Skane University Hospital: collaborator

Study Sites (1)

Karolinska Hospital, Solna

Stockholm, 17176, Sweden

Location

Related Publications (4)

• Hayden JM, Oras J, Block L, Thorn SE, Palmqvist C, Salehi S, Nordstrom JL, Gupta A. Intraperitoneal ropivacaine reduces time interval to initiation of chemotherapy after surgery for advanced ovarian cancer: randomised controlled double-blind pilot study. Br J Anaesth. 2020 May;124(5):562-570. doi: 10.1016/j.bja.2020.01.026. Epub 2020 Mar 13.

  PMID: 32172954 BACKGROUND

• Hasselgren E, Kofoed NG, Falconer H, Bjorne H, Zach D, Hunde D, Johansson H, Asp M, Thorlacius K, Kannisto P, Salehi S. Prospective Assessment of Clinically Relevant Fluid Balance Thresholds Associated With Postoperative Complications in Advanced Ovarian Cancer. Acta Anaesthesiol Scand. 2025 Oct;69(9):e70112. doi: 10.1111/aas.70112.

  PMID: 40856042 DERIVED

• Gultekin O, Gonzalez-Molina J, Sarhan D, Groes-Kofoed N, Hassan MU, Lehti K, Salehi S. Systemic and tumor-specific inflammatory markers VCAM-1 and ICAM-1 as indicators of extent of surgery and oncologic outcome in advanced ovarian cancer. Transl Oncol. 2025 Sep;59:102462. doi: 10.1016/j.tranon.2025.102462. Epub 2025 Jul 12.

  PMID: 40652770 DERIVED

• Hasselgren E, Groes-Kofoed N, Falconer H, Bjorne H, Zach D, Hunde D, Johansson H, Asp M, Kannisto P, Gupta A, Salehi S. Effect of intraperitoneal ropivacaine during and after cytoreductive surgery on time-interval to adjuvant chemotherapy in advanced ovarian cancer: a randomised, double-blind phase III trial. Br J Anaesth. 2025 Mar;134(3):662-670. doi: 10.1016/j.bja.2024.10.015. Epub 2024 Nov 20.

  PMID: 39572271 DERIVED

MeSH Terms

Interventions

Ropivacaine; Saline Solution

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Sahar Salehi, MD, PhD

  Karolinska Institute and Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study drugs are blinded and administered perioperatively. Fully blinded for all (participants, assessors etc)
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant, Assistant Professor

Model Details: Randomised, double blind, prospective, multicenter

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 22, 2019
• Study Start: August 26, 2020
• Primary Completion: January 10, 2024
• Study Completion (Estimated): August 26, 2028
• Last Updated: January 11, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)