Cryptococcal MeningitisPhase 4COATNCT01075152

Cryptococcal Optimal ART Timing Trial

A Phase 4 study testing efavirenz and nucleoside in people with Cryptococcal Meningitis and HIV Infections, run by University of Minnesota at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The Cryptococcal Optimal ART Timing (COAT) trial seeks to determine after cryptococcal meningitis (CM) whether early initiation of antiretroviral therapy (ART) prior to hospital discharge results in superior survival compared to standard initiation of ART started as an outpatient. Read more about this study

Who is it for?: Ages 14 years and older
Conditions the study is for: Cryptococcal Meningitis, HIV Infections, AIDS
What is being tested?: efavirenz and nucleoside
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 177 participants
Where: 3 sitesin 2 countries
Study dates: Nov 2010to Mar 2013
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 14 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

HIV-infection, documented by ELISA
Antiretroviral medication naïve (excluding mother-to-child transmission therapy)
Age >14 years
Cryptococcal meningitis diagnosed by either culture or CSF cryptococcal antigen (CRAG)
Ability and willingness of the participant or legal guardian/representative to give informed consent.
Receiving amphotericin-based anti-fungal therapy

Who cannot join

Study entry prior to receipt of <7 days or >11 days of amphotericin therapy
History of prior, known cryptococcal meningitis
Inability to take enteral medication
Receiving chemotherapy or other immunosuppressant medications
Cannot or unlikely to attend regular clinic visits
Contraindication to immediate or delayed HIV therapy based on serious co-morbidities or co-infections, or laboratory values
Pregnancy or Breastfeeding
Female participants of childbearing potential who are participating in sexual activity that could lead to pregnancy must agree to use two reliable methods of contraception

Trial locations and contacts

3 sites in 2 countries.

Country

City, postcode or hospital

3 sites in 2 countries

Uganda2 sites

Infectious Disease Institute, Mulago Hospital, Makerere University
Kampala
Mbarara University of Science and Technology
Mbarara

Other trials in Uganda

South Africa1 site

GF Jooste Hospital
Cape Town

Other trials in South Africa

About this study

Official title: Trial for the Optimal Timing of HIV Therapy After Cryptococcal Meningitis

Read the detailed description

After 7-11 days of amphotericin B therapy, subjects will be randomized in a 1:1 allocation to:

Early initiation of ART (Experimental Group) = ART initiated within 48 hours after study entry, OR
Standard initiation of ART (Control Group) = ART at >=4 weeks after study entry

HIV therapy will be with efavirenz plus nucleoside backbone per national guidelines for first line therapy.

Conditions: Cryptococcal Meningitis, HIV Infections, AIDS
Being tested: efavirenz, nucleoside
Keywords: cryptococcal meningitis, cryptococcus, cryptococcosis, HIV, AIDS, strategy
Medical subject headings: Meningitis, Cryptococcal, HIV Infections, Acquired Immunodeficiency Syndrome, Cryptococcosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

efavirenzDrug
Also called sustiva
Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.
nucleosideBiological
Also called zidovudine or stavudine, lamivudine
Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.

Study groups in NCT01075152
Study group	Role	What they receive
Earlier HIV Therapy	Experimental	HIV therapy initiated at 7-13 days of cryptococcal meningitis diagnosis. HIV therapy consisting of a nucleoside with lamivudine and efavirenz. Receives: Drug: efavirenz; Biological: nucleoside
Deferred HIV Therapy	Active comparator	HIV therapy initiated at 5 weeks after cryptococcal meningitis diagnosis (+/- 1 week). HIV therapy consisting of a nucleoside with lamivudine and efavirenz. Receives: Drug: efavirenz; Biological: nucleoside

What is being measured

The primary outcome is the main question the study is designed to answer.

Mortality
Intention to treat analysis of 26 week survival of all subjects enrolled. Reported below are the numbers of participants who died by Week 26.
Measured: 26 weeks from study entry

Secondary outcomes (8)

Incidence of Immune Reconstitution Inflammatory Syndrome
Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 46 weeks after enrollment.
Measured: 46 weeks
Incidence of Cryptococcal-relapse
Incidence of culture positive cryptococcal meningitis relapse
Measured: 46 weeks
Safety of ART Initiation
Incidence of Adverse Events (Grade 3,4,5) through 46-weeks, as defined by the National Institute of Allergy and Infectious Diseases, Division of AIDS toxicity classification scale, version 2009.
Measured: 46 weeks
46-week Survival
46-week survival by time-to-event analysis of all subjects enrolled
Measured: 46 weeks
HIV-1 Viral Suppression
HIV-1 virologic suppression to <400 copies/mL at 26-weeks after enrollment
Measured: 26 weeks
Antiretroviral Therapy Tolerability
Incidence of antiretroviral therapy interruption by >=3 consecutive days
Measured: 26 weeks
Karnofsky Functional Status
Functional status via Karnofsky performance status score at 4, 26, 46 weeks.
Karnofsky Scale:
100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of his personal needs.
50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent.
20 - Very sick; hospital admission necessary; active supportive treatment necessary.
10 - Moribund; fatal processes progressing rapidly. 0 - Dead
Measured: 46 weeks
Microbiologic Clearance
Microbiologic clearance of cryptococcus as measured by serial quantitative cryptococcal cultures collected at diagnosis through 14 days of amphotericin therapy. The early fungicidal activity (EFA) of the rate of clearance is expressed as log10 colony forming units (CFU) of Cryptococcus neoformans per mL of CSF per day.
Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2010Mar 2013

First posted24 Feb 2010 (estimated)
Study startNov 2010
Primary completionOct 2012
Study completionMar 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (21)Papers the sponsor has linked to this study.
Other trials for Cryptococcal MeningitisStudies of the same condition, open and under way.
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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 177 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01075152
Sponsor's protocol ID: 0810M49622
Other IDs: U01AI089244
Acronym: COAT
Status last verified: Jun 2020
First submitted: 23 Feb 2010
Last updated: 9 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Rajasingham R, Williams D, Meya DB, Meintjes G, Boulware DR, Scriven J. Nosocomial drug-resistant bacteremia in 2 cohorts with cryptococcal meningitis, Africa. Emerg Infect Dis. 2014 Apr;20(4):722-4. doi: 10.3201/eid2004.131277. No abstract available.
PubMed 24655747
Carlson RD, Rolfes MA, Birkenkamp KE, Nakasujja N, Rajasingham R, Meya DB, Boulware DR. Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study. Metab Brain Dis. 2014 Jun;29(2):269-279. doi: 10.1007/s11011-013-9476-1. Epub 2014 Jan 9.
PubMed 24399496
Boulware DR, Rolfes MA, Rajasingham R, von Hohenberg M, Qin Z, Taseera K, Schutz C, Kwizera R, Butler EK, Meintjes G, Muzoora C, Bischof JC, Meya DB. Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast. Emerg Infect Dis. 2014 Jan;20(1):45-53. doi: 10.3201/eid2001.130906.
PubMed 24378231
Kabanda T, Siedner MJ, Klausner JD, Muzoora C, Boulware DR. Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid. Clin Infect Dis. 2014 Jan;58(1):113-6. doi: 10.1093/cid/cit641. Epub 2013 Sep 24.
PubMed 24065327
Robertson EJ, Najjuka G, Rolfes MA, Akampurira A, Jain N, Anantharanjit J, von Hohenberg M, Tassieri M, Carlsson A, Meya DB, Harrison TS, Fries BC, Boulware DR, Bicanic T. Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis. J Infect Dis. 2014 Jan 1;209(1):74-82. doi: 10.1093/infdis/jit435. Epub 2013 Aug 14.
PubMed 23945372
Durski KN, Kuntz KM, Yasukawa K, Virnig BA, Meya DB, Boulware DR. Cost-effective diagnostic checklists for meningitis in resource-limited settings. J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):e101-8. doi: 10.1097/QAI.0b013e31828e1e56.
PubMed 23466647
Rajasingham R, Rolfes MA, Birkenkamp KE, Meya DB, Boulware DR. Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis. PLoS Med. 2012;9(9):e1001316. doi: 10.1371/journal.pmed.1001316. Epub 2012 Sep 25.
PubMed 23055838
Rolfes MA, Hullsiek KH, Rhein J, Nabeta HW, Taseera K, Schutz C, Musubire A, Rajasingham R, Williams DA, Thienemann F, Muzoora C, Meintjes G, Meya DB, Boulware DR. The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis. Clin Infect Dis. 2014 Dec 1;59(11):1607-14. doi: 10.1093/cid/ciu596. Epub 2014 Jul 23.
PubMed 25057102
Scriven JE, Rhein J, Hullsiek KH, von Hohenberg M, Linder G, Rolfes MA, Williams DA, Taseera K, Meya DB, Meintjes G, Boulware DR; COAT Team. Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial. J Infect Dis. 2015 Sep 1;212(5):769-78. doi: 10.1093/infdis/jiv067. Epub 2015 Feb 4.
PubMed 25651842
Williams DA, Kiiza T, Kwizera R, Kiggundu R, Velamakanni S, Meya DB, Rhein J, Boulware DR. Evaluation of fingerstick cryptococcal antigen lateral flow assay in HIV-infected persons: a diagnostic accuracy study. Clin Infect Dis. 2015 Aug 1;61(3):464-7. doi: 10.1093/cid/civ263. Epub 2015 Apr 1.
PubMed 25838287
Rajasingham R, Rhein J, Klammer K, Musubire A, Nabeta H, Akampurira A, Mossel EC, Williams DA, Boxrud DJ, Crabtree MB, Miller BR, Rolfes MA, Tengsupakul S, Andama AO, Meya DB, Boulware DR. Epidemiology of meningitis in an HIV-infected Ugandan cohort. Am J Trop Med Hyg. 2015 Feb;92(2):274-9. doi: 10.4269/ajtmh.14-0452. Epub 2014 Nov 10.
PubMed 25385864
Nabeta HW, Bahr NC, Rhein J, Fossland N, Kiragga AN, Meya DB, Dunlop SJ, Boulware DR. Accuracy of noninvasive intraocular pressure or optic nerve sheath diameter measurements for predicting elevated intracranial pressure in cryptococcal meningitis. Open Forum Infect Dis. 2014 Oct 11;1(3):ofu093. doi: 10.1093/ofid/ofu093. eCollection 2014 Dec.
PubMed 25734161
Meya DB, Okurut S, Zziwa G, Rolfes MA, Kelsey M, Cose S, Joloba M, Naluyima P, Palmer BE, Kambugu A, Mayanja-Kizza H, Bohjanen PR, Eller MA, Wahl SM, Boulware DR, Manabe YC, Janoff EN. Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune reconstitution inflammatory syndrome. J Infect Dis. 2015 May 15;211(10):1597-606. doi: 10.1093/infdis/jiu664. Epub 2014 Dec 9.
PubMed 25492918
Bahr NC, Rolfes MA, Musubire A, Nabeta H, Williams DA, Rhein J, Kambugu A, Meya DB, Boulware DR. Standardized electrolyte supplementation and fluid management improves survival during amphotericin therapy for cryptococcal meningitis in resource-limited settings. Open Forum Infect Dis. 2014 Aug 25;1(2):ofu070. doi: 10.1093/ofid/ofu070. eCollection 2014 Sep.
PubMed 25734140
Kwizera R, Nguna J, Kiragga A, Nakavuma J, Rajasingham R, Boulware DR, Meya DB. Performance of cryptococcal antigen lateral flow assay using saliva in Ugandans with CD4 <100. PLoS One. 2014 Jul 31;9(7):e103156. doi: 10.1371/journal.pone.0103156. eCollection 2014.
PubMed 25078453

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Cryptococcal Infection, Cryptococcal Pneumonia
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Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
Idiopathic CD4+ Lymphocytopenia, Cryptococcal Meningitis
Not yet recruitingPhase 3
Optimizing Care for Cryptococcal Antigenemia: Evaluation of Short Course Fluconazole and ART Timing Among CrAg+ Persons With Low Titers
Cryptococcal Antigenemia, HIV-1-infection
RecruitingPhase 2/3
Platform Trial For Cryptococcal Meningitis (PLATFORM-CM)
Hiv, Cryptococcal Meningitis
RecruitingPhase 2/3
Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia
Cryptococcal Meningitis

All Cryptococcal Meningitis trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Trial for the Optimal Timing of HIV Therapy After Cryptococcal Meningitis
ClinicalTrials.gov ID: NCT01075152
Acronym / sponsor ID: COAT / 0810M49622
Conditions: Cryptococcal Meningitis, HIV Infections, AIDS
Keywords: cryptococcal meningitis, cryptococcus, cryptococcosis, HIV, AIDS, strategy
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 177 participants (actual)
Lead sponsor: University of MinnesotaUniversity, hospital or other
Collaborators: Mbarara University of Science and Technology, Makerere University, National Institute of Allergy and Infectious Diseases (NIAID), University of Cape Town
Study start: Nov 2010
Primary completion: Oct 2012 (actual)
Study completion: Mar 2013 (actual)
First posted: 24 Feb 2010 (estimated)
Results: Posted 20 Aug 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

After 7-11 days of amphotericin B therapy, subjects will be randomized in a 1:1 allocation to:

Early initiation of ART (Experimental Group) = ART initiated within 48 hours after study entry, OR
Standard initiation of ART (Control Group) = ART at >=4 weeks after study entry

HIV therapy will be with efavirenz plus nucleoside backbone per national guidelines for first line therapy.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Earlier HIV Therapy	Experimental	Drug: efavirenz, Biological: nucleosideHIV therapy initiated at 7-13 days of cryptococcal meningitis diagnosis. HIV therapy consisting of a nucleoside with lamivudine and efavirenz.
Deferred HIV Therapy	Active comparator	Drug: efavirenz, Biological: nucleosideHIV therapy initiated at 5 weeks after cryptococcal meningitis diagnosis (+/- 1 week). HIV therapy consisting of a nucleoside with lamivudine and efavirenz.

Who may qualify

Ages: 14 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (6 listed)

HIV-infection, documented by ELISA
Antiretroviral medication naïve (excluding mother-to-child transmission therapy)
Age >14 years
Cryptococcal meningitis diagnosed by either culture or CSF cryptococcal antigen (CRAG)
Ability and willingness of the participant or legal guardian/representative to give informed consent.

Key exclusion criteria (8 listed)

Study entry prior to receipt of <7 days or >11 days of amphotericin therapy
History of prior, known cryptococcal meningitis
Inability to take enteral medication
Receiving chemotherapy or other immunosuppressant medications
Cannot or unlikely to attend regular clinic visits

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
efavirenzAlso: sustivaTreatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.	Drug	Deferred HIV Therapy, Earlier HIV Therapy
nucleosideAlso: zidovudine or stavudine, lamivudineTreatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.	Biological	Deferred HIV Therapy, Earlier HIV Therapy

Primary outcome

Mortality
Time frame: 26 weeks from study entry
Intention to treat analysis of 26 week survival of all subjects enrolled. Reported below are the numbers of participants who died by Week 26.

8 secondary outcomes

Incidence of Immune Reconstitution Inflammatory Syndrome
Time frame: 46 weeks
Incidence of Cryptococcal-relapse
Time frame: 46 weeks
Safety of ART Initiation
Time frame: 46 weeks
46-week Survival
Time frame: 46 weeks
HIV-1 Viral Suppression
Time frame: 26 weeks
Antiretroviral Therapy Tolerability
Time frame: 26 weeks
Karnofsky Functional Status
Time frame: 46 weeks
Microbiologic Clearance
Time frame: 4 weeks

Results and safety

Results posted to the registry on 20 Aug 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Earlier HIV Therapy	88	87
Deferred HIV Therapy	89	89

Primary outcome: Mortality

Time frame: 26 weeks from study entry. Number. Unit: participants

Measure	Earlier HIV Therapy n = 88	Deferred HIV Therapy n = 89
Value	40	27

Earlier HIV Therapy vs Deferred HIV Therapy: Hazard Ratio (HR): 1.73 (95% CI 1.06 to 2.82), p = 0.03, Regression, Cox

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: 46 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Earlier HIV Therapy	49 of 88 (55.7%)	73 of 88 (83%)	Not reported
Deferred HIV Therapy	53 of 89 (59.6%)	75 of 89 (84.3%)	Not reported

Limitations and caveats (from the sponsor): The differences in mortality in the two arms were of sufficient magnitude that trial enrollment was stopped early by the Data and Safety Monitoring Board. Historically, trials stopped early routinely over-estimate the magnitude of benefit or harm.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24655747Rajasingham R, Williams D, Meya DB, Meintjes G, Boulware DR, Scriven J. Nosocomial drug-resistant bacteremia in 2 cohorts with cryptococcal meningitis, Africa. Emerg Infect Dis. 2014 Apr;20(4):722-4. doi: 10.3201/eid2004.131277. No abstract available.
Background: PubMed 24399496Carlson RD, Rolfes MA, Birkenkamp KE, Nakasujja N, Rajasingham R, Meya DB, Boulware DR. Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study. Metab Brain Dis. 2014 Jun;29(2):269-279. doi: 10.1007/s11011-013-9476-1. Epub 2014 Jan 9.
Background: PubMed 24378231Boulware DR, Rolfes MA, Rajasingham R, von Hohenberg M, Qin Z, Taseera K, Schutz C, Kwizera R, Butler EK, Meintjes G, Muzoora C, Bischof JC, Meya DB. Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast. Emerg Infect Dis. 2014 Jan;20(1):45-53. doi: 10.3201/eid2001.130906.
Background: PubMed 24065327Kabanda T, Siedner MJ, Klausner JD, Muzoora C, Boulware DR. Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid. Clin Infect Dis. 2014 Jan;58(1):113-6. doi: 10.1093/cid/cit641. Epub 2013 Sep 24.
Background: PubMed 23945372Robertson EJ, Najjuka G, Rolfes MA, Akampurira A, Jain N, Anantharanjit J, von Hohenberg M, Tassieri M, Carlsson A, Meya DB, Harrison TS, Fries BC, Boulware DR, Bicanic T. Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis. J Infect Dis. 2014 Jan 1;209(1):74-82. doi: 10.1093/infdis/jit435. Epub 2013 Aug 14.
Background: PubMed 23466647Durski KN, Kuntz KM, Yasukawa K, Virnig BA, Meya DB, Boulware DR. Cost-effective diagnostic checklists for meningitis in resource-limited settings. J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):e101-8. doi: 10.1097/QAI.0b013e31828e1e56.
Background: PubMed 23055838Rajasingham R, Rolfes MA, Birkenkamp KE, Meya DB, Boulware DR. Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis. PLoS Med. 2012;9(9):e1001316. doi: 10.1371/journal.pmed.1001316. Epub 2012 Sep 25.
Background: PubMed 25057102Rolfes MA, Hullsiek KH, Rhein J, Nabeta HW, Taseera K, Schutz C, Musubire A, Rajasingham R, Williams DA, Thienemann F, Muzoora C, Meintjes G, Meya DB, Boulware DR. The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis. Clin Infect Dis. 2014 Dec 1;59(11):1607-14. doi: 10.1093/cid/ciu596. Epub 2014 Jul 23.
Background: PubMed 25651842Scriven JE, Rhein J, Hullsiek KH, von Hohenberg M, Linder G, Rolfes MA, Williams DA, Taseera K, Meya DB, Meintjes G, Boulware DR; COAT Team. Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial. J Infect Dis. 2015 Sep 1;212(5):769-78. doi: 10.1093/infdis/jiv067. Epub 2015 Feb 4.
Background: PubMed 25838287Williams DA, Kiiza T, Kwizera R, Kiggundu R, Velamakanni S, Meya DB, Rhein J, Boulware DR. Evaluation of fingerstick cryptococcal antigen lateral flow assay in HIV-infected persons: a diagnostic accuracy study. Clin Infect Dis. 2015 Aug 1;61(3):464-7. doi: 10.1093/cid/civ263. Epub 2015 Apr 1.
Background: PubMed 25385864Rajasingham R, Rhein J, Klammer K, Musubire A, Nabeta H, Akampurira A, Mossel EC, Williams DA, Boxrud DJ, Crabtree MB, Miller BR, Rolfes MA, Tengsupakul S, Andama AO, Meya DB, Boulware DR. Epidemiology of meningitis in an HIV-infected Ugandan cohort. Am J Trop Med Hyg. 2015 Feb;92(2):274-9. doi: 10.4269/ajtmh.14-0452. Epub 2014 Nov 10.
Background: PubMed 25734161Nabeta HW, Bahr NC, Rhein J, Fossland N, Kiragga AN, Meya DB, Dunlop SJ, Boulware DR. Accuracy of noninvasive intraocular pressure or optic nerve sheath diameter measurements for predicting elevated intracranial pressure in cryptococcal meningitis. Open Forum Infect Dis. 2014 Oct 11;1(3):ofu093. doi: 10.1093/ofid/ofu093. eCollection 2014 Dec.
NIH NIAID FAQ on COAT Trial (Preliminary Results)Link provided by the sponsor.

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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.

David R Boulware, MD, MPH principal investigator

University of Minnesota

3 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing efavirenz and nucleoside in people with Cryptococcal Meningitis and HIV Infections, run by University of Minnesota at 3 sites in 2 countries.

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 8 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 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Uganda, South Africa. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Mortality (time frame: 26 weeks from study entry). 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 NCT01075152, which also lists 21 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 9 Jun 2020.