Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

PREVAIL VII: Persistence of Ebola Virus in Aqueous Humor and Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03309020
Recruitment Status : Completed
First Posted : October 13, 2017
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )

Tracking Information
First Submitted Date October 12, 2017
First Posted Date October 13, 2017
Last Update Posted Date August 19, 2019
Actual Study Start Date September 5, 2018
Actual Primary Completion Date August 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 16, 2019)
  • The proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue [ Time Frame: Study completion ]
    Study CRFs capture the grade of anterior chamber cells for each eye according to the SUN criteria. Regression models will be fit with these grades as outcome variables and survivor status, age (less than 40 or greater than or equal to 40) and gender as explanatory variables. The test of the hypothesis of no difference in grade according to survivor status will be conducted by testing the null hypothesis that the regression coefficient associated with survivor status is zero. This will be conducted at the one and three month assessments. A significance level of 0.025 will be used for both tests to account for test multiplicity.
  • Comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. [ Time Frame: 1 month and 3 months ]
    The secondary outcome about having 20/40 or better BCVA after surgery will be conducted using logistic regression with explanatory variables gender, age and survivor status.
Original Primary Outcome Measures
 (submitted: October 12, 2017)
  • The proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue [ Time Frame: Study completion ]
  • Comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. [ Time Frame: 1 month and 3 months ]
Change History Complete list of historical versions of study NCT03309020 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: August 16, 2019)
  • Proportion of survivors with at least 20/40 best corrected visual acuity after cataract surgery, relative to controls [ Time Frame: Study completion ]
    Proportion of survivors with at least 20/40 best corrected visual acuity after cataract surgery, relative to controls
  • Post-operative optical coherence tomography results in EVD survivors [ Time Frame: Study completion ]
    Post-operative optical coherence tomography results in EVD survivors
  • Significance of covariates, age and gender, in logistic regression assessment of viral persistence and cataract outcomes [ Time Frame: Study completion ]
    Significance of covariates, age and gender, in logistic regression assessment of viral persistence and cataract outcomes
Original Secondary Outcome Measures
 (submitted: October 12, 2017)
  • Proportion of survivors with at least 20/40 best corrected visual acuity after cataract surgery, relative to controls [ Time Frame: Study completion ]
  • Post-operative optical coherence tomography results in EVD survivors [ Time Frame: Study completion ]
  • Significance of covariates, age and gender, in logistic regression assessment of viral persistence and cataract outcomes [ Time Frame: Study completion ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title PREVAIL VII: Persistence of Ebola Virus in Aqueous Humor and Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease
Official Title PREVAIL VII: Persistence of Ebola Virus in Aqueous Humor and Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease
Brief Summary

Objective: Zaire ebolavirus is a single-stranded RNA virus associated with high morbidity and mortality. The most recent epidemic of Ebola virus disease (EVD) in West Africa resulted in over 11,000 deaths and disabling sequelae among survivors, among which eye complications are highly represented. Chronic intraocular inflammation and viral persistence may result in posterior synechiae and cataract formation, resulting in loss of visual acuity and requiring surgical intervention to resolve. Approximately one out of ten Ebola survivors present with cataract, most of whom will require intraocular surgery during their lifetime, and many of whom require intervention in the near future to regain quality of life. For survivors who are blind from cataract, cataract extraction is necessary to restore visual function, allow reintegration into society and facilitate performance of activities of daily living.

However, surgical parameters among Ebola survivors are unknown, including whether Ebola viral RNA persists in aqueous humor, whether additional anti-inflammatory medication is needed, and the expected degree of improvement in visual function. Moreover, sites of viral persistence are unknown, and it is unclear if lens tissues removed during cataract surgery may harbor virus in Ebola-affected eyes. We propose following EVD survivors and control subjects undergoing cataract surgery to determine visual outcomes among Ebola survivors and explore detection of the presence of virus in lens tissues. The data will inform both future surgical intervention and aid in the understanding of the pathophysiology of Ebola-associated eye disease.

Study Population: Up to 60 Ebola survivors and up to 60 controls will be enrolled. The accrual ceiling is 120 participants.

Design: This is a prospective, natural history study to evaluate the persistence of Ebola viral RNA in the eyes of Ebola survivors and assess the response to cataract surgery in survivors as compared to controls. EVD survivors will first undergo assessment of aqueous humor for the presence of viral RNA. Survivors testing negative for viral RNA and control subjects will undergo clinically indicated cataract surgery. Subjects will be evaluated 1 day, 1 week, 1 month, 3 months, and 6 months after surgery for safety and visual outcome assessments, and more often as clinically indicated.

Outcome Measures: The primary outcomes are: 1) the proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue and 2) the comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. Secondary outcomes include: 1) the proportion of survivors with at least 20/40 best corrected visual acuity (BCVA) after cataract surgery, relative to controls; 2) significance of covariates, age and gender, in logistic regression assessment of viral persistence and cataract outcomes; 3) post-operative optical coherence tomography results in EVD survivors.

Detailed Description

Objective: Zaire ebolavirus is a single-stranded RNA virus associated with high morbidity and mortality. The most recent epidemic of Ebola virus disease (EVD) in West Africa resulted in over 11,000 deaths and disabling sequelae among survivors, among which eye complications are highly represented. Chronic intraocular inflammation and viral persistence may result in posterior synechiae and cataract formation, resulting in loss of visual acuity and requiring surgical intervention to resolve. Approximately one out of ten Ebola survivors present with cataract, most of whom will require intraocular surgery during their lifetime, and many of whom require intervention in the near future to regain quality of life. For survivors who are blind from cataract, cataract extraction is necessary to restore visual function, allow reintegration into society and facilitate performance of activities of daily living.

However, surgical parameters among Ebola survivors are unknown, including whether Ebola viral RNA persists in aqueous humor, whether additional anti-inflammatory medication is needed, and the expected degree of improvement in visual function. Moreover, sites of viral persistence are unknown, and it is unclear if lens tissues removed during cataract surgery may harbor virus in Ebola-affected eyes. We propose following EVD survivors and control subjects undergoing cataract surgery to determine visual outcomes among Ebola survivors and explore detection of the presence of virus in lens tissues. The data will inform both future surgical intervention and aid in the understanding of the pathophysiology of Ebola-associated eye disease.

Study Population: Up to 60 Ebola survivors and up to 60 controls will be enrolled. The accrual ceiling is 120 participants.

Design: This is a prospective, natural history study to evaluate the persistence of Ebola viral RNA in the eyes of Ebola survivors and assess the response to cataract surgery in survivors as compared to controls. EVD survivors will first undergo assessment of aqueous humor for the presence of viral RNA. Survivors testing negative for viral RNA and control subjects will undergo clinically indicated cataract surgery. Subjects will be evaluated 1 day, 1 week, 1 month, and 3, 6, 9 and 12 months after surgery for safety and visual outcome assessments, and more often as clinically indicated.

Outcome Measures: The primary outcomes are: 1) the proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue and 2) the comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. Secondary outcomes include: 1) the proportion of survivors with at least 20/40 best corrected visual acuity (BCVA) after cataract surgery, relative to controls; 2) impact the of covariates, age and gender on viral persistence and cataract outcomes; 3) post-operative optical coherence tomography results in EVD survivors.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Ebola survivors and controls will be recruited from the ongoing PREVAIL III study using the PREVAIL Social Mobilization and Communications team and Participant Trackers who are assigned to follow individual subjects. Ebola survivors may also be recruited from other survivor care clinics in Liberia, such as ELWA Hospital and their outreach clinics, research programs, or be self-referred.@@@@@@
Condition Cataract
Intervention Not Provided
Study Groups/Cohorts
  • Controls
    Control participants
  • Ebola Survivors
    Participants who have survived Ebola
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: August 7, 2019)
37
Original Estimated Enrollment
 (submitted: October 12, 2017)
120
Actual Study Completion Date August 1, 2019
Actual Primary Completion Date August 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria
  • INCLUSION CRITERIA:

To be eligible, the following inclusion criteria must be met, where applicable.

  1. Participant must be 14 years of age or older.
  2. Participant must be able to understand and sign an informed consent or have a parent/legal guardian do so if they are minor children or a legally authorized representative to provide consent for adults without consent capacity.
  3. Participant must be either:

    • an Ebola virus disease (EVD) seropositive survivor or seropositive control OR
    • an EVD seronegative survivor or seronegative control (Serology confirmation is available for PREVAIL participants and will be conducted for non-PREVAIL participants.).
  4. Participant must have visually significant cataract(s) consistent with level of visual deficit.
  5. Participant must have corrected visual acuity worse than 20/40 in affected eye and vision loss believed to be primarily the result of the cataract.
  6. Any woman and persons of childbearing potential age have a negative pregnancy test at screening and must be willing to undergo pregnancy testing prior to the cataract surgery.

EXCLUSION CRITERIA:

A participant is not eligible if any of the following exclusion criteria are present.

  1. Concurrent life-threatening illness or other condition that compromises a participant s ability to safely undergo surgery, as determined by the surgical and medical team, including any condition that prevents the participant from lying down supine or remaining still, such as severe lung disease, or a known life-threatening, untreated or unstable cardiac or pulmonary condition.
  2. Active uveitis at time of surgery or within the past three months, if documented.
  3. Participant is pregnant, as surgery is elective and no adequate data regarding the use of postoperative topical antibiotic-steroid combination drops exists in pregnant women.
  4. Any condition that poses a risk to the participant having a safe surgical or post-operative experience, including known inability or unwillingness to follow up for the full duration of the protocol.
Sex/Gender
Sexes Eligible for Study: All
Ages 14 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Liberia
Removed Location Countries  
 
Administrative Information
NCT Number NCT03309020
Other Study ID Numbers 999917167
17-EI-N167
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
Study Sponsor National Eye Institute (NEI)
Collaborators Not Provided
Investigators
Principal Investigator: Rachel J Bishop, M.D. National Eye Institute (NEI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date August 1, 2019