Contribution of Contrast Enhanced Ultrasound for Diagnosis of Adnexal Torsion

NCT06677554 | Recruiting Phase 3

• 1 other identifier: 2021PI162
• Study Type: interventional
• Target: 256
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Adnexal Torsion

Outcome Measures

Primary Outcomes (1)

• Evaluation of the two-stage diagnostic strategy effectiveness

  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

Study Arms (2)

ultrasound with contrast injection

EXPERIMENTAL

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®)

Control

ACTIVE COMPARATOR

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)

Interventions

Addition of ultrasound with contrast injection (SonoVue®) DRUG

Addition of contrast evaluation with SonoVue® injection (5 min including 1 min of acquisition) within the diagnostic strategy

ultrasound with contrast injection

Standard Care (in control arm) OTHER

No addition of ultrasound with contrast

Control

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (6)

CHU

Besançon, France

NOT YET RECRUITING

CHU

Dijon, France

NOT YET RECRUITING

CHRU Nancy - Maternité Régionale

Nancy, France

RECRUITING

CHU

Reims, France

NOT YET RECRUITING

CMCO

Schiltigheim, France

NOT YET RECRUITING

CHU Hautepierre

Strasbourg, France

NOT YET RECRUITING

Related Publications (1)

• Fijean AL, Manhertz D, Massicot L, Lecointre L, Mottet N, Raimond E, Simon E, Gabriele V, Morel O, Beaumont M, Hossu G, Bertholdt C. Contribution of contrast-enhanced ultrasound for diagnosis of adnexal torsion (COVARIAN): protocol for a randomised controlled trial. BMJ Open. 2026 Feb 25;16(2):e110352. doi: 10.1136/bmjopen-2025-110352.

  PMID: 41748169 BACKGROUND

MeSH Terms

Conditions

Ovarian Torsion

Interventions

Contrast Media; contrast agent BR1; Standard of Care

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Torsion Abnormality; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Charline BERTHOLDT, Pr

  CHRU Nancy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charline BERTHOLDT, Pr

CONTACT

+33 383 344 312; c.bertholdt@chru-nancy.fr

Dorine MANHERTZ, MSc

CONTACT

d.manhertz@chru-nancy.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 6, 2024
• Study Start: May 14, 2025
• Primary Completion (Estimated): February 7, 2028
• Study Completion (Estimated): February 7, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)