NCT06677554: COVARIAN

Contribution of Contrast Enhanced Ultrasound for Diagnosis of Adnexal Torsion

Recruiting now Phase 3 Last updated 8 April 2026

What this trial tests

Phase 3 trial testing Addition of ultrasound with contrast injection (SonoVue®) in Adnexal Torsion in 256 participants. Currently enrolling.

Timeline

14 May 2025

Primary endpoint
7 February 2028

7 February 2028

Quick facts

Lead sponsor	Central Hospital, Nancy, France
Phase	Phase 3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	diagnostic
Enrollment	256
Start date	14 May 2025
Primary completion	7 February 2028
Estimated completion	7 February 2028
Sites	6 locations across France

Drugs / interventions tested

• Addition of ultrasound with contrast injection (SonoVue®) — full drug profile →
• Standard Care (in control arm) — full drug profile →

Conditions studied

• Adnexal Torsion — all drugs for Adnexal Torsion →

Sponsor

Central Hospital, Nancy, France

Who can join

18 and older, female only, with Adnexal Torsion. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Contribution of contrast-enhanced ultrasound for diagnosis of adnexal torsion (COVARIAN): protocol for a randomised controlled trial.
   Fijean AL, Manhertz D, Massicot L, Lecointre L, et al · · 2026 · PMID 41748169 · DOI 10.1136/bmjopen-2025-110352
2. Application of ultrasound in combination with other methods in gynecological disease: artificial intelligence, surgery, and drugs.
   Shi S, Dai C, Liu D, Liu X. · · 2025 · PMID 40958876 · DOI 10.3389/fonc.2025.1567024