West Nile Fever With Neurologic Manifestation (Diagnosis)Phase 3NCT06590207
Convalescent Plasma for the Treatment of Patients With WNV - a Double- Blind Randomized Controlled Study
A Phase 3 study testing plasma rich with WNV neutralizing antibodies and Saline in people with West Nile Fever With Neurologic Manifestation (Diagnosis) and West Nile Fever Without Complications, run by Sheba Medical Center at 1 site in Israel.
Trial summary
Name of the study: Administering neutralizing convalescent plasma to hospitalized patients with West Nile fever - a double-blind randomized controlled study. The purpose of this study is to test the safety and effectiveness of giving blood plasma from convalescents rich in neutralizers as treatment against West Nile… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- West Nile Fever With Neurologic Manifestation (Diagnosis), West Nile Fever Without Complications
- What is being tested?
- plasma rich with WNV neutralizing antibodies and Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteIsrael
- Study dates
- 4 Jul 2024to 30 Mar 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hospitalized patients with positive WNV-PCR with fever/neurological symptoms, and 72 hours have not yet passed since the positive result.
- Age 60 or older.
- Age over 18 and younger than 60 with immunosuppression (hypogammaglobulinemia, solid organ transplants, bone marrow transplants, hemato-oncological malignancies).
Who cannot join
- Age younger than 60 without immunosuppression.
- More than 72 hours have passed since the diagnosis of West Nile fever.
- Pregnant women. Criteria for exclusion from the experiment: none Reference to the inclusion of pregnant women, special populations - children and those lacking judgment- not relevant: excludes pregnant women and special populations
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Administering Convalescent Plasma Rich With Neutralizing Abs. to Hospitalized Adults With WNV - a Double-blind Randomized Controlled Study
Name of the study:
Administering neutralizing convalescent plasma to hospitalized patients with West Nile fever - a double-blind randomized controlled study.
The purpose of this study is to test the safety and effectiveness of giving blood plasma from convalescents rich in neutralizers as treatment against West Nile fever.
Read the detailed description
The study is performed in Sheba Medical Center ( and will be expanded in the soon future to other Medical centers in Israel).
Hospitalized patients diagnosed by blood/CSF PCR or IgM, with West Nile Virus will be recruited to the study.
After signing an informed consent they will be randomized (2:1) to receive either blood plasma rich in neutralizing antibodies or saline as placebo.
Number of participants in this center: 130 Age range: 60 years old and older, 18-60 years old with immunosuppression.
Inclusion criteria:
- Hospitalized patients with positive WNV-PCR with fever/neurological symptoms, and 72 hours have not yet passed since the positive result.
- Age 60 or older.
- Age over 18 and younger than 60 with immunosuppression (hypogammaglobulinemia, solid organ transplants, bone marrow transplants, hemato-oncological malignancies).
Exclusion criteria:
- Age younger than 60 without immunosuppression.
- More than 72 hours have passed since the diagnosis of West Nile fever.
- Pregnant women.
Reference to the inclusion of pregnant women, special populations - children and those lacking judgment- not relevant: excludes pregnant women and special populations.
The duration of the medical trial includes the follow-up period after the trial:
The duration of the treatment is one day, single dose of plasma/saline. The follow-up period is 90 days.
The clinical follow-up plan (during and at the end of the treatment):
A total of 10 visits will be conducted. On day 1, the following will be performed: screening, Medical history \& Physical examination, IV Convalescent Plasma vs. Saline, Urine and blood for PCR, functional \& neurologic assesment, IgG and IgM from serum, blood test for CBC \& renal function.
On day 2-7 and 30 and 90, AE will be collected. On day 3, 5, 7 Urine and blood for PCR will be collected. Neurologic assesment will be conducted on all visits. Serology will be collected also on day 30 and 90.
After discharge, a follow-up visit will be performed either by a visit to the clinic or via phone call.
- Conditions
- West Nile Fever With Neurologic Manifestation (Diagnosis), West Nile Fever Without Complications
- Being tested
- plasma rich with WNV neutralizing antibodies, Saline
- Keywords
- WNV; Neutralizing Abs; Convalescent plasma; neuroinvasive
- Medical subject headings
- Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
plasma rich with WNV neutralizing antibodiesDrug
Also called Neurtalizing plasma
200 ml plasma of the convalescents: produced in the blood bank, from the blood of Sheba workers who participated in the SPRI study (Helsinki 0196-23) and whose blood was found to have neutralizing antibodies to WNV above 1:524. The blood units from the volunteers who will donate will meet all the requirements of a normal blood donation and will only include men or women who were not pregnant, and the units will pass all the tests accepted at the blood bank before donation.
SalineDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 200ml of neutralizing plasma | Experimental | The plasma of the convalescents: produced in the blood bank of Sheba Medical Center, from the blood of Sheba workers who participated in the SPRI study (Helsinki 0196-23) and whose blood was found to have neutralizing antibodies to WNV (above 1:524). The blood units from the volunteers who will donate will meet all the requirements of a normal blood donation and will only include men or women who were not pregnant, and the units will pass all the tests accepted at the blood bank before donation. Receives: Drug: plasma rich with WNV neutralizing antibodies |
| Saline | Placebo comparator | 200 ml Saline Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unfavorable outcom = Composite outcome of mortality or functional deterioration on day 30
functional deterioration will be defined using Barthel Index
Measured: day 28-32
Secondary outcomes (5)
unfavorable outcome on day 90
same as primary outcome but on day 90
Measured: day 88-92
Serious adverse events
Allergic reaction, pulmonary congestion, hemolysis
Measured: day 2-32
Mortality
Mortality by day 90
Measured: day 28-92
Functional deterioration by day 30 & 90
decrease in Barthel index from pre-infection baseline
Measured: 28-92 days
Neurologic deterioration by day 30 & 90
combined neurologic score of Barthel index, glasgow outcome score and modified minimental score
Measured: 28-92 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start4 Jul 2024
- Primary completion31 Jan 2025
- Study completion30 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for West Nile Fever With Neurologic Manifestation (Diagnosis)Studies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- double-blind randomized controlled study.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Gili Regev-Yochay MD, Sheba Medical Center
- Investigators
- Michaela Va Smilovici-Ofir, Phd, Study chair, Sheba research grants and academic collaboration director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06590207
- Sponsor's protocol ID
- 1381-24-SMC
- Status last verified
- Jul 2024
- First submitted
- 31 Jul 2024
- Last updated
- 29 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bassal R, Shohat T, Kaufman Z, Mannasse B, Shinar E, Amichay D, Barak M, Ben-Dor A, Bar Haim A, Cohen D, Mendelson E, Lustig Y. The seroprevalence of West Nile Virus in Israel: A nationwide cross sectional study. PLoS One. 2017 Jun 16;12(6):e0179774. doi: 10.1371/journal.pone.0179774. eCollection 2017.
PubMed 28622360Planitzer CB, Modrof J, Kreil TR. West Nile virus neutralization by US plasma-derived immunoglobulin products. J Infect Dis. 2007 Aug 1;196(3):435-40. doi: 10.1086/519392. Epub 2007 Jun 18.
PubMed 17597458Srivastava R, Ramakrishna C, Cantin E. Anti-inflammatory activity of intravenous immunoglobulins protects against West Nile virus encephalitis. J Gen Virol. 2015 Jun;96(Pt 6):1347-1357. doi: 10.1099/vir.0.000079. Epub 2015 Feb 9.
PubMed 25667322Gnann JW Jr, Agrawal A, Hart J, Buitrago M, Carson P, Hanfelt-Goade D, Tyler K, Spotkov J, Freifeld A, Moore T, Reyno J, Masur H, Jester P, Dale I, Li Y, Aban I, Lakeman FD, Whitley RJ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Lack of Efficacy of High-Titered Immunoglobulin in Patients with West Nile Virus Central Nervous System Disease. Emerg Infect Dis. 2019 Nov;25(11):2064-2073. doi: 10.3201/eid2511.190537.
PubMed 31625835Mbonde AA, Gritsch D, Harahsheh EY, Kasule SN, Hasan S, Parsons AM, Zhang N, Butterfield R, Shiue H, Norville KA, Reynolds JL, Vikram HR, Chong B, Grill MF. Neuroinvasive West Nile Virus Infection in Immunosuppressed and Immunocompetent Adults. JAMA Netw Open. 2024 Mar 4;7(3):e244294. doi: 10.1001/jamanetworkopen.2024.4294.
PubMed 38546642Regev-Yochay G, Barda N, Shusterman Y, Magiel E, Ganmore I, Baharav N, Belkin A, Margalit I, Indenbaum V, Lustig Y, Weiss-Ottolenghi Y, Joseph G, Tomer E, Maggio N, Canetti M, Yonath H, Leshem E, Levy I, Peretz Y, Amit S, Miller L, Misgav M, Landa N, Shinar E, Brod M, Wieder-Finesod A, Harats D, Yahav D. West Nile Virus-Neutralizing Plasma for West Nile Virus Disease. NEJM Evid. 2026 Apr;5(4):EVIDoa2500169. doi: 10.1056/EVIDoa2500169. Epub 2026 Mar 24.
PubMed 41874260
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administering Convalescent Plasma Rich With Neutralizing Abs. to Hospitalized Adults With WNV - a Double-blind Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT06590207
- Acronym / sponsor ID
- 1381-24-SMC
- Conditions
- West Nile Fever With Neurologic Manifestation (Diagnosis), West Nile Fever Without Complications
- Keywords
- WNV; Neutralizing Abs; Convalescent plasma; neuroinvasive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 4 Jul 2024 (actual)
- Primary completion
- 31 Jan 2025 (actual)
- Study completion
- 30 Mar 2025 (actual)
- First posted
- 19 Sep 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.
Name of the study:
Administering neutralizing convalescent plasma to hospitalized patients with West Nile fever - a double-blind randomized controlled study.
The purpose of this study is to test the safety and effectiveness of giving blood plasma from convalescents rich in neutralizers as treatment against West Nile fever.
Detailed description
The study is performed in Sheba Medical Center ( and will be expanded in the soon future to other Medical centers in Israel).
Hospitalized patients diagnosed by blood/CSF PCR or IgM, with West Nile Virus will be recruited to the study.
After signing an informed consent they will be randomized (2:1) to receive either blood plasma rich in neutralizing antibodies or saline as placebo.
Number of participants in this center: 130 Age range: 60 years old and older, 18-60 years old with immunosuppression.
Inclusion criteria:
- Hospitalized patients with positive WNV-PCR with fever/neurological symptoms, and 72 hours have not yet passed since the positive result.
- Age 60 or older.
- Age over 18 and younger than 60 with immunosuppression (hypogammaglobulinemia, solid organ transplants, bone marrow transplants, hemato-oncological malignancies).
Exclusion criteria:
- Age younger than 60 without immunosuppression.
- More than 72 hours have passed since the diagnosis of West Nile fever.
- Pregnant women.
Reference to the inclusion of pregnant women, special populations - children and those lacking judgment- not relevant: excludes pregnant women and special populations.
The duration of the medical trial includes the follow-up period after the trial:
The duration of the treatment is one day, single dose of plasma/saline. The follow-up period is 90 days.
The clinical follow-up plan (during and at the end of the treatment):
A total of 10 visits will be conducted. On day 1, the following will be performed: screening, Medical history \& Physical examination, IV Convalescent Plasma vs. Saline, Urine and blood for PCR, functional \& neurologic assesment, IgG and IgM from serum, blood test for CBC \& renal function.
On day 2-7 and 30 and 90, AE will be collected. On day 3, 5, 7 Urine and blood for PCR will be collected. Neurologic assesment will be conducted on all visits. Serology will be collected also on day 30 and 90.
After discharge, a follow-up visit will be performed either by a visit to the clinic or via phone call.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- double-blind randomized controlled study.
| Arm | Type | Receives |
|---|---|---|
| 200ml of neutralizing plasma | Experimental | Drug: plasma rich with WNV neutralizing antibodiesThe plasma of the convalescents: produced in the blood bank of Sheba Medical Center, from the blood of Sheba workers who participated in the SPRI study (Helsinki 0196-23) and whose blood was found to have neutralizing antibodies to WNV (above 1:524). The blood units from the volunteers who will donate will meet all the requirements of a normal blood donation and will only include men or women who were not pregnant, and the units will pass all the tests accepted at the blood bank before donation. |
| Saline | Placebo comparator | Drug: Saline200 ml Saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Hospitalized patients with positive WNV-PCR with fever/neurological symptoms, and 72 hours have not yet passed since the positive result.
- Age 60 or older.
- Age over 18 and younger than 60 with immunosuppression (hypogammaglobulinemia, solid organ transplants, bone marrow transplants, hemato-oncological malignancies).
Key exclusion criteria (3 listed)
- Age younger than 60 without immunosuppression.
- More than 72 hours have passed since the diagnosis of West Nile fever.
- Pregnant women. Criteria for exclusion from the experiment: none Reference to the inclusion of pregnant women, special populations - children and those lacking judgment- not relevant: excludes pregnant women and special populations
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 |
|---|---|---|
| plasma rich with WNV neutralizing antibodiesAlso: Neurtalizing plasma200 ml plasma of the convalescents: produced in the blood bank, from the blood of Sheba workers who participated in the SPRI study (Helsinki 0196-23) and whose blood was found to have neutralizing antibodies to WNV above 1:524. The blood units from the volunteers who will donate will meet all the requirements of a normal blood donation and will only include men or women who were not pregnant, and the units will pass all the tests accepted at the blood bank before donation. | Drug | 200ml of neutralizing plasma |
| SalinePlacebo | Drug | Saline |
Primary outcome
Unfavorable outcom = Composite outcome of mortality or functional deterioration on day 30
Time frame: day 28-32
functional deterioration will be defined using Barthel Index
5 secondary outcomes
unfavorable outcome on day 90
Time frame: day 88-92
Serious adverse events
Time frame: day 2-32
Mortality
Time frame: day 28-92
Functional deterioration by day 30 & 90
Time frame: 28-92 days
Neurologic deterioration by day 30 & 90
Time frame: 28-92 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
- Background: PubMed 28622360Bassal R, Shohat T, Kaufman Z, Mannasse B, Shinar E, Amichay D, Barak M, Ben-Dor A, Bar Haim A, Cohen D, Mendelson E, Lustig Y. The seroprevalence of West Nile Virus in Israel: A nationwide cross sectional study. PLoS One. 2017 Jun 16;12(6):e0179774. doi: 10.1371/journal.pone.0179774. eCollection 2017.
- Background: PubMed 17597458Planitzer CB, Modrof J, Kreil TR. West Nile virus neutralization by US plasma-derived immunoglobulin products. J Infect Dis. 2007 Aug 1;196(3):435-40. doi: 10.1086/519392. Epub 2007 Jun 18.
- Background: PubMed 25667322Srivastava R, Ramakrishna C, Cantin E. Anti-inflammatory activity of intravenous immunoglobulins protects against West Nile virus encephalitis. J Gen Virol. 2015 Jun;96(Pt 6):1347-1357. doi: 10.1099/vir.0.000079. Epub 2015 Feb 9.
- Background: PubMed 31625835Gnann JW Jr, Agrawal A, Hart J, Buitrago M, Carson P, Hanfelt-Goade D, Tyler K, Spotkov J, Freifeld A, Moore T, Reyno J, Masur H, Jester P, Dale I, Li Y, Aban I, Lakeman FD, Whitley RJ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Lack of Efficacy of High-Titered Immunoglobulin in Patients with West Nile Virus Central Nervous System Disease. Emerg Infect Dis. 2019 Nov;25(11):2064-2073. doi: 10.3201/eid2511.190537.
- Background: PubMed 38546642Mbonde AA, Gritsch D, Harahsheh EY, Kasule SN, Hasan S, Parsons AM, Zhang N, Butterfield R, Shiue H, Norville KA, Reynolds JL, Vikram HR, Chong B, Grill MF. Neuroinvasive West Nile Virus Infection in Immunosuppressed and Immunocompetent Adults. JAMA Netw Open. 2024 Mar 4;7(3):e244294. doi: 10.1001/jamanetworkopen.2024.4294.
- Derived from this study: PubMed 41874260Regev-Yochay G, Barda N, Shusterman Y, Magiel E, Ganmore I, Baharav N, Belkin A, Margalit I, Indenbaum V, Lustig Y, Weiss-Ottolenghi Y, Joseph G, Tomer E, Maggio N, Canetti M, Yonath H, Leshem E, Levy I, Peretz Y, Amit S, Miller L, Misgav M, Landa N, Shinar E, Brod M, Wieder-Finesod A, Harats D, Yahav D. West Nile Virus-Neutralizing Plasma for West Nile Virus Disease. NEJM Evid. 2026 Apr;5(4):EVIDoa2500169. doi: 10.1056/EVIDoa2500169. Epub 2026 Mar 24.
- 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. This study is not recruiting at the moment.
Michaela Va Smilovici-Ofir, Phd study chair
Sheba research grants and academic collaboration director
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing plasma rich with WNV neutralizing antibodies and Saline in people with West Nile Fever With Neurologic Manifestation (Diagnosis) and West Nile Fever Without Complications, run by Sheba Medical Center at 1 site in Israel.
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 3 inclusion and 3 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: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Unfavorable outcom = Composite outcome of mortality or functional deterioration on day 30 (time frame: day 28-32). 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 NCT06590207, which also lists 6 linked publications.
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 29 Apr 2025.