Adnexal TorsionPhase 3COVARIANNCT06677554
Contribution of Contrast Enhanced Ultrasound for Diagnosis of Adnexal Torsion
A Phase 3 study testing Addition of ultrasound with contrast injection (SonoVue®) in people with Adnexal Torsion, run by Central Hospital, Nancy, France at 6 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Adnexal Torsion
- What is being tested?
- Addition of ultrasound with contrast injection (SonoVue®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 256 participants
- Where
- 6 sitesFrance
- Study dates
- 14 May 2025to 7 Feb 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Dorine MANHERTZ, MSc contact
6 sites in 1 country
France6 sites, 6 recruiting
- Not yet recruiting
CHU
Besançon
MOTTET Nicolas, Pr, +33381218505, n1mottet@chu-besancon.fr
Nicolas MOTTET, Pr
- Not yet recruiting
CHU
Dijon
Emmanuel SIMON, Pr, +33380293852, emmanuel.simon@chu-dijon.fr
Emmanuel SIMON, Pr
- Recruiting
CHRU Nancy - Maternité Régionale
Nancy
Charline BERTHOLDT, Pr, +33 383 344 312, c.bertholdt@chru-nancy.fr
Charline BERTHOLDT, Pr
- Not yet recruiting
CHU
Reims
Emilie Raimond, +33326789598, eraimond@chu-reims.fr
Emilie RAIMOND
- Not yet recruiting
CMCO
Schiltigheim
Victor GABRIELE, +33369553404, victor.gabriele@chru-strasbourg.fr
Victor GABRIELE
- Not yet recruiting
CHU Hautepierre
Strasbourg
Lise LECOINTRE, +33388127472, lise.lecointre@chru-strasbourg.fr
Lise LECOINTRE
About this study
Official title: 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%).
Read more
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
- Being tested
- Addition of ultrasound with contrast injection (SonoVue®), Standard Care (in control arm)
- Medical subject headings
- Ovarian Torsion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
Standard Care (in control arm)Other
No addition of ultrasound with contrast
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Other: Standard Care (in control arm) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 38 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2024
- Study start14 May 2025
- Primary completion7 Feb 2028 (estimated)
- Study completion7 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adnexal TorsionStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 256 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, BERTHOLDT Charline, Central Hospital, Nancy, France
- Investigators
- Charline BERTHOLDT, Pr, Principal investigator, CHRU Nancy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06677554
- Sponsor's protocol ID
- 2021PI162
- Acronym
- COVARIAN
- Status last verified
- Apr 2026
- First submitted
- 5 Nov 2024
- Last updated
- 8 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41748169
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COVARIAN - Contribution of Contrast Enhanced Ultrasound for Diagnosis of Adnexal Torsion: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06677554
- Acronym / sponsor ID
- COVARIAN / 2021PI162
- Conditions
- Adnexal Torsion
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 256 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 14 May 2025 (actual)
- Primary completion
- 7 Feb 2028 (estimated)
- Study completion
- 7 Feb 2028 (estimated)
- First posted
- 6 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ultrasound with contrast injection | Experimental | Drug: Addition of ultrasound with contrast injection (SonoVue®)Patients consulting the gynecological emergencies as part of the management of a strong suspicion of adnexal torsion (after the clinical examination and standard ultrasound) |
| Control | Active comparator | Other: Standard Care (in control arm)Patients consulting the gynecological emergencies as part of the management of a strong suspicion of adnexal torsion (after the clinical examination and standard ultrasound) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (19 listed)
- Person who does not understand and/or speak French
- Any medical situation that does not indicate the administration of SonoVue®, including:
- History of PEG allergy (or macrogol)
- Person referred to in Articles 10, 31, 32, 33 and 34 of Regulation EU 536/2014:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | ultrasound with contrast injection |
| Standard Care (in control arm)No addition of ultrasound with contrast | Other | Control |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2026.
- Background: PubMed 41748169Fijean 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dorine MANHERTZ, MSc contact
Charline BERTHOLDT, Pr principal investigator
CHRU Nancy
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Addition of ultrasound with contrast injection (SonoVue®) in people with Adnexal Torsion, run by Central Hospital, Nancy, France at 6 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Charline BERTHOLDT, Pr (+33 383 344 312, c.bertholdt@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of the two-stage diagnostic strategy effectiveness (time frame: 38 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06677554, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2026.