Contribution of Contrast Enhanced Ultrasound for Diagnosis of Adnexal Torsion (COVARIAN)

April 2, 2026 updated by: BERTHOLDT Charline, Central Hospital, Nancy, France

COVARIAN - Contribution of Contrast Enhanced Ultrasound for Diagnosis of Adnexal Torsion: a Randomized Controlled Trial

Adnexal torsion is the rotation of the ovary around its vascular axis resulting, in the absence of treatment, ischemia that can lead to peritonitis by necrosis or impaired fertility. It is a gynecological emergency affecting 3% of women of childbearing age, including from adolescence, and requires surgical treatment as soon as possible, classically within 6 hours.

The symptomatology of adnexal torsion is dominated by pelvic pain of sudden onset and variable intensity, an aspecific sign that does not allow a diagnosis of certainty. There are no biological markers and, in the context of the emergency, the only imaging examination available is pelvic ultrasound associated with a Doppler flow analysis but with a low and variable diagnostic performance depending on the studies (sensitivity variable from 46 to 73%).

There are currently no tests that can provide a diagnosis of certainty. Only surgical exploration, carried out at the discretion of the practitioner on the basis of a bundle of arguments, can confirm or refute the diagnosis. However, this management strategy leads to the realization of emergency surgical interventions wrongly since 3 out of 10 women will finally not have an adnexal torsion (PMSI data from participating centers: 30 to 45% false positives).

Contrast ultrasound is a technique that uses a strict intravascular product to assess the vascularization of the ovary and offers a high diagnostic performance in the context of adnexal torsion. Indeed, a retrospective study, published in 2021, reports a sensitivity of 94% and a specificity of 100%. The preliminary results of our pilot study (AGATA APJC 2019, Dr Bertholdt, NCT04522219) also go in this direction with a sensitivity of 100%, a specificity of 86% and a negative predictive value of 100% (data being published).

The COVARIAN project, second stage of the AGATA project, aims to demonstrate that the addition of a contrast evaluation to standard ultrasound in the diagnostic strategy in case of suspicion of adnexal torsion improves the health of women by reducing the rate of wrongly surgery, that is, without proven torsion.

COVARIAN will be the first prospective multicenter randomized study evaluating the direct benefit for women of using ultrasound contrast evaluation in the management strategy in case of suspicion of adnexal torsion.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

256

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Besançon, France
        • Not yet recruiting
        • CHU
        • Contact:
        • Principal Investigator:
          • Nicolas MOTTET, Pr
      • Dijon, France
        • Not yet recruiting
        • CHU
        • Contact:
        • Principal Investigator:
          • Emmanuel SIMON, Pr
      • Nancy, France
        • Recruiting
        • CHRU Nancy - Maternité Régionale
        • Contact:
        • Principal Investigator:
          • Charline BERTHOLDT, Pr
      • Reims, France
        • Not yet recruiting
        • CHU
        • Contact:
        • Principal Investigator:
          • Emilie RAIMOND
      • Schiltigheim, France
      • Strasbourg, France
        • Not yet recruiting
        • CHU Hautepierre
        • Contact:
        • Principal Investigator:
          • Lise LECOINTRE

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 or over
  • Person who has carried out a preliminary clinical examination adapted to the clinical trial
  • Strong suspicion of adnexal torsion with surgery planned
  • No ongoing pregnancy or breastfeeding
  • Affiliation to or beneficiary of a social security scheme
  • Person who has received complete information on the organization of the research and has signed their informed consent

Exclusion Criteria:

  • Person who does not understand and/or speak French

  • Any medical situation that does not indicate the administration of SonoVue®, including:

    • Known hypersensitivity to sulphur hexafluoride or any of the other components of SonoVue
    • Woman with acute coronary syndrome or unstable ischemic heart disease
    • Woman with acute endocarditis
    • Woman with valve prostheses
    • Women with acute systemic inflammatory disease and/or sepsis
    • Woman with hypercoagulation and/or recent thromboembolic accident
    • End-stage woman with kidney or liver disease
    • Woman with right-left shunt, severe pulmonary hypertension (pulmonary arterial pressure > 90 mmHg)
    • Women with uncontrolled systemic hypertension
    • Woman with respiratory distress syndrome
    • Medical condition contraindicating the administration of SonoVue®,
  • History of PEG allergy (or macrogol)

  • Person referred to in Articles 10, 31, 32, 33 and 34 of Regulation EU 536/2014:

    • Pregnant, parturient or breastfeeding/nursing mother
    • Minor (not emancipated)
    • Adult subject to a legal protection measure (guardianship, curatorship, safeguarding of justice)
    • Person of legal age who is unable to express consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ultrasound with contrast injection
Patients consulting the gynecological emergencies as part of the management of a strong suspicion of adnexal torsion (after the clinical examination and standard ultrasound)
Drug: Addition of ultrasound with contrast injection (SonoVue®)
Addition of contrast evaluation with SonoVue® injection (5 min including 1 min of acquisition) within the diagnostic strategy
Active Comparator: Control
Patients consulting the gynecological emergencies as part of the management of a strong suspicion of adnexal torsion (after the clinical examination and standard ultrasound)
Other: Standard Care (in control arm)
No addition of ultrasound with contrast

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the two-stage diagnostic strategy effectiveness
Time Frame: 38 months
Percentage of surgical procedures performed in emergency (within 6 hours of arrival of the patient) without proven torsion (no visible spiral turn in intraoperative) in each group.
38 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Central Hospital, Nancy, France

Investigators

  • Principal Investigator: Charline BERTHOLDT, Pr, Chru Nancy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2025

Primary Completion (Estimated)

February 7, 2028

Study Completion (Estimated)

February 7, 2028

Study Registration Dates

First Submitted

November 5, 2024

First Submitted That Met QC Criteria

November 5, 2024

First Posted (Actual)

November 6, 2024

Study Record Updates

Last Update Posted (Actual)

April 8, 2026

Last Update Submitted That Met QC Criteria

April 2, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021PI162

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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