Visceral LeishmaniasisPhase 4LVBrasilNCT01310738
Efficacy and Safety Study of Drugs for Treatment of Visceral Leishmaniasis in Brazil
A Phase 4 study testing Antimoniate of N-methylglucamine, amphotericin B deoxycholate and Liposomal amphotericin B in people with Visceral Leishmaniasis, run by University of Brasilia at 5 sites in Brazil.
Trial summary
This study is aimed to compare the efficacy and safety of medications currently used in Brazil for treatment of visceral leishmaniasis. The investigators will compare the effects of meglumine antimoniate, two formulations of amphotericin B: deoxycholate and liposomal, and a combination of meglumine plus the liposomal… Read more about this study
- Who is it for?
- Ages 6 months to 50 years
- Conditions the study is for
- Visceral Leishmaniasis
- What is being tested?
- Antimoniate of N-methylglucamine, amphotericin B deoxycholate and Liposomal amphotericin B
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 378 participants
- Where
- 5 sitesBrazil
- Study dates
- Feb 2011to Feb 2015
- Phase
- Phase 4
- 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 6 months to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- patients with visceral leishmaniasis characterized by fever plus hepatomegaly or splenomegaly with at least one positive result in the following laboratory tests:
- direct observation of leishmania amastigotes in bone marrow smear
- leishmania in vitro culture from bone marrow aspirates
- leishmania kDNA amplification by PCR in bone marrow or peripheral blood samples
- rK39 immunochromatographic rapid test performed on serum sample
Who cannot join
- pregnancy
- HIV infection
- chronic diseases such as diabetes mellitus,kidney, liver or cardiac diseases, schistosomiasis, malaria or tuberculosis
- immune disorders or use of drugs which interferes with the immune response
- treatment with drugs with increased risk for toxicity associated with the study drugs
- exposure to antileishmanial drugs during the past six months
Show all 11Show fewer
- I.V. drug users
- episodes of visceral leishmaniasis relapse
- hypersensibility to the study drugs
- difficulties for accomplishing the follow-up schedule
- any of the following clinical signs of laboratory abnormalities: hepatic encephalopathy, generalized edema, toxemic individuals, severe malnutrition, jaundice, abnormal serum creatinine, bilirubin, INR > 2,0, platelet count < 20000/mm3
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Brazil5 sites
Hospital Infantil João Paulo II - FHEMIG
Belo Horizonte, Minas Gerais, 30130-110
Hospital São José de Doenças Infecciosas
Fortaleza, Ceará, 60455610
Hospital Universitário Clemente de Faria - Universidade Estadual de Montes Claros
Montes Claros, Minas Gerais, 39401-002
Hospital Universitário da Universidade Federal de Sergipe
Sergipe, Aracaju, 49060-100
Hospital de Doencas Infecto Contagiosas - HDIC
Teresina, Piauí, 64001450
About this study
Official title: Multicentric Efficacy and Safety Study of Antileishmanial Drugs for Treatment of Visceral Leishmaniasis in Brazil
This study is aimed to compare the efficacy and safety of medications currently used in Brazil for treatment of visceral leishmaniasis. The investigators will compare the effects of meglumine antimoniate, two formulations of amphotericin B: deoxycholate and liposomal, and a combination of meglumine plus the liposomal amphotericin B formulation. The study is designed to demonstrate the difference in efficacy measured as cure rate at six months after treatment and the safety profile based on the adverse event rate observed with each intervention.
Read the detailed description
Visceral leishmaniasis is a relevant public health problem in Brazil with approximately 3500 cases registered every year. Eight percent lethality rate has been observed during the past decade in spite of free of charge availability of antileishmanial drugs supplied by the public health system.
The present study was designed as a phase IV, multicentric, open label, active controlled clinical trial targeted to visceral leishmaniasis adult and pediatric cases.
The current drugs approved for visceral leishmaniasis treatment in Brazil will be compared in four treatment groups: meglumine antimoniate, amphotericin B deoxycholate, liposomal amphotericin B and a combination of single dose of liposomal amphotericin B plus meglumine antimoniate. Meglumine antimoniate treated patients will constitute the active control group.
Drugs will be compared based on the cure rate observed after six months follow-up.
The study arm submitted to treatment with Amphotericin B deoxycholate was suspended in September 2012.
- Conditions
- Visceral Leishmaniasis
- Being tested
- Antimoniate of N-methylglucamine, amphotericin B deoxycholate, Liposomal amphotericin B
- Keywords
- Visceral leishmaniasis, Leishmania infantum, Leishmania chagasi
- Medical subject headings
- Leishmaniasis, Visceral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antimoniate of N-methylglucamineDrug
Also called Glucantime
Antimoniate of N-methyl glucamine 20mg/kg/d of pentavalent antimonial, I.V. for 20 consecutive days.
amphotericin B deoxycholateDrug
Also called Fungizone, Anforicin B
1mg/kg/d, I.V. for 14 consecutive days.
Liposomal amphotericin BDrug
Also called AmBisome
3mg/kg/d, I.V. for 7 consecutive days.
Liposomal amphotericin BDrug
Also called AmBisome
10mg/kg/d, I.V. single dose.
Antimoniate of N-methylglucamineDrug
Also called Glucantime
20mg/kg/d of pentavalent antimonial I.V. for 10 days
| Study group | Role | What they receive |
|---|---|---|
| Meglumine antimoniate | Active comparator | Antimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days. Receives: Drug: Antimoniate of N-methylglucamine |
| Liposomal Amphotericin B | Experimental | Liposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days. Receives: Drug: Liposomal amphotericin B |
| Amphotericin B | Experimental | Amphotericin B deoxycholate 1mg/kg/d I.V. for 14 consecutive days. This arm was suspended in September 19th, 2012, because of a relevant excess of adverse events and serious adverse events associated with this experimental intervention in comparison with the active comparator and the other two experimental arms. The suspension of this study arm was supported by a DSMB statement. Receives: Drug: amphotericin B deoxycholate |
| Combination therapy | Experimental | Liposomal amphotericin B 10mg/kg/d, I.V. single dose on day 0 plus Antimoniate of N-methylglucamine 20mg/kg/d for 10 consecutive days on days 1 to 10. Receives: Drug: Liposomal amphotericin B; Drug: Antimoniate of N-methylglucamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cure rate
Complete remission of clinical signs and symptoms, three months after treatment plus normal hematological lab evaluation and no relapse at sixth month follow-up.
Measured: 6 month
Secondary outcomes (4)
Improvement rate
Fever disappearing, stable or improving hematological lab abnormalities plus any spleen size reduction.
Measured: 30 days
Relapse rate
Reappearing of signs and symptoms after any improvement observed after treatment, during the six months follow-up period.
Measured: (6 months post treatment) After treatment until the sixth month of follow-up
Serious adverse events rate
Rate of adverse events defined as conditions which fulfilled any of the following: results in death, is life threatening, requires inpatient hospitalization or prolongs hospitalization, results in persistent or significant disability/incapacity, causes a congenital anomaly or birth defect or it is considered as a important medical event for the responsible clinician.
Measured: During (day one) and within the six months follow-up
Adverse event rate and intensity
Cumulative rate of any adverse event, including clinical, laboratory and electrocardiographic abnormalities observed within the treatment and follow-up periods. All adverse events will be graded using an adapted ACTG 0-4 scale.
Measured: During (day one) treatment and within the six months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2011 (estimated)
- Study startFeb 2011
- Primary completionOct 2014
- Study completionFeb 2015
Why it stopped: DSMB recommendation based on programmed interim analysis.
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 Visceral LeishmaniasisStudies 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
- None (open label)
- Enrolment
- 378 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Brasilia
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Brazil, Drugs for Neglected Diseases, Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Responsible party
- Principal investigator, Gustavo Adolfo Sierra Romero, University of Brasilia
- Investigators
- Carlos HN Costa, MD PhD, Principal investigator, Federal University of PiauiDorcas L Costa, MD PhD, Principal investigator, Federal University of PiauiAna LT Rabello, MD PhD, Principal investigator, Centro de Pesquisas Rene Rachou - Fiocruz - Minas GeraisSilvio FG de Carvalho, MD PhD, Principal investigator, Montes Claros State University - UnimontesAndrea L de Carvalho, MD, Principal investigator, Hospital Infantil Joao Paulo II - FHEMIGRoque P de Almeida, MD PhD, Principal investigator, Federal University of SergipeFabiana P Alves, MD PhD, Study director, Drugs for Neglected DiseasesGustavo AS Romero, MD PhD, Study chair, University of Brasilia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01310738
- Sponsor's protocol ID
- LVBrasil_2007
- Other IDs
- 559819/2010-2, 108042500, CAAE 0973.1.000.245-10
- Acronym
- LVBrasil
- Status last verified
- Aug 2017
- First submitted
- 7 Mar 2011
- Last updated
- 5 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Romero GAS, Costa DL, Costa CHN, de Almeida RP, de Melo EV, de Carvalho SFG, Rabello A, de Carvalho AL, Sousa AQ, Leite RD, Lima SS, Amaral TA, Alves FP, Rode J; Collaborative LVBrasil Group. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial. PLoS Negl Trop Dis. 2017 Jun 29;11(6):e0005706. doi: 10.1371/journal.pntd.0005706. eCollection 2017 Jun.
PubMed 28662034
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentric Efficacy and Safety Study of Antileishmanial Drugs for Treatment of Visceral Leishmaniasis in Brazil
- ClinicalTrials.gov ID
- NCT01310738
- Acronym / sponsor ID
- LVBrasil / LVBrasil_2007
- Conditions
- Visceral Leishmaniasis
- Keywords
- Visceral leishmaniasis, Leishmania infantum, Leishmania chagasi
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: DSMB recommendation based on programmed interim analysis.
- Enrolment
- 378 participants (actual)
- Lead sponsor
- University of BrasiliaUniversity, hospital or other
- Collaborators
- Ministry of Health, Brazil, Drugs for Neglected Diseases, Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Study start
- Feb 2011
- Primary completion
- Oct 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 8 Mar 2011 (estimated)
- 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.
This study is aimed to compare the efficacy and safety of medications currently used in Brazil for treatment of visceral leishmaniasis. The investigators will compare the effects of meglumine antimoniate, two formulations of amphotericin B: deoxycholate and liposomal, and a combination of meglumine plus the liposomal amphotericin B formulation. The study is designed to demonstrate the difference in efficacy measured as cure rate at six months after treatment and the safety profile based on the adverse event rate observed with each intervention.
Detailed description
Visceral leishmaniasis is a relevant public health problem in Brazil with approximately 3500 cases registered every year. Eight percent lethality rate has been observed during the past decade in spite of free of charge availability of antileishmanial drugs supplied by the public health system.
The present study was designed as a phase IV, multicentric, open label, active controlled clinical trial targeted to visceral leishmaniasis adult and pediatric cases.
The current drugs approved for visceral leishmaniasis treatment in Brazil will be compared in four treatment groups: meglumine antimoniate, amphotericin B deoxycholate, liposomal amphotericin B and a combination of single dose of liposomal amphotericin B plus meglumine antimoniate. Meglumine antimoniate treated patients will constitute the active control group.
Drugs will be compared based on the cure rate observed after six months follow-up.
The study arm submitted to treatment with Amphotericin B deoxycholate was suspended in September 2012.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Meglumine antimoniate | Active comparator | Drug: Antimoniate of N-methylglucamineAntimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days. |
| Liposomal Amphotericin B | Experimental | Drug: Liposomal amphotericin BLiposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days. |
| Amphotericin B | Experimental | Drug: amphotericin B deoxycholateAmphotericin B deoxycholate 1mg/kg/d I.V. for 14 consecutive days. This arm was suspended in September 19th, 2012, because of a relevant excess of adverse events and serious adverse events associated with this experimental intervention in comparison with the active comparator and the other two experimental arms. The suspension of this study arm was supported by a DSMB statement. |
| Combination therapy | Experimental | Drug: Liposomal amphotericin B, Drug: Antimoniate of N-methylglucamineLiposomal amphotericin B 10mg/kg/d, I.V. single dose on day 0 plus Antimoniate of N-methylglucamine 20mg/kg/d for 10 consecutive days on days 1 to 10. |
Who may qualify
- Ages
- 6 months to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- patients with visceral leishmaniasis characterized by fever plus hepatomegaly or splenomegaly with at least one positive result in the following laboratory tests:
- direct observation of leishmania amastigotes in bone marrow smear
- leishmania in vitro culture from bone marrow aspirates
- leishmania kDNA amplification by PCR in bone marrow or peripheral blood samples
- rK39 immunochromatographic rapid test performed on serum sample
Key exclusion criteria (11 listed)
- pregnancy
- HIV infection
- chronic diseases such as diabetes mellitus,kidney, liver or cardiac diseases, schistosomiasis, malaria or tuberculosis
- immune disorders or use of drugs which interferes with the immune response
- treatment with drugs with increased risk for toxicity associated with the study drugs
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 |
|---|---|---|
| Antimoniate of N-methylglucamineAlso: GlucantimeAntimoniate of N-methyl glucamine 20mg/kg/d of pentavalent antimonial, I.V. for 20 consecutive days. | Drug | Meglumine antimoniate |
| amphotericin B deoxycholateAlso: Fungizone, Anforicin B1mg/kg/d, I.V. for 14 consecutive days. | Drug | Amphotericin B |
| Liposomal amphotericin BAlso: AmBisome3mg/kg/d, I.V. for 7 consecutive days. | Drug | Liposomal Amphotericin B |
| Liposomal amphotericin BAlso: AmBisome10mg/kg/d, I.V. single dose. | Drug | Combination therapy |
| Antimoniate of N-methylglucamineAlso: Glucantime20mg/kg/d of pentavalent antimonial I.V. for 10 days | Drug | Combination therapy |
Primary outcome
Cure rate
Time frame: 6 month
Complete remission of clinical signs and symptoms, three months after treatment plus normal hematological lab evaluation and no relapse at sixth month follow-up.
4 secondary outcomes
Improvement rate
Time frame: 30 days
Relapse rate
Time frame: (6 months post treatment) After treatment until the sixth month of follow-up
Serious adverse events rate
Time frame: During (day one) and within the six months follow-up
Adverse event rate and intensity
Time frame: During (day one) treatment and within the six months follow-up
Results and safety
The study was stopped early (reason given: DSMB recommendation based on programmed interim analysis.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2017.
- Results publication: PubMed 28662034Romero GAS, Costa DL, Costa CHN, de Almeida RP, de Melo EV, de Carvalho SFG, Rabello A, de Carvalho AL, Sousa AQ, Leite RD, Lima SS, Amaral TA, Alves FP, Rode J; Collaborative LVBrasil Group. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial. PLoS Negl Trop Dis. 2017 Jun 29;11(6):e0005706. doi: 10.1371/journal.pntd.0005706. eCollection 2017 Jun.
- Individual participant dataSharing planned: Undecided
Related trials for Visceral Leishmaniasis
RecruitingObservational study
Diagnosis and Treatment of Leishmania Infections
Kinetoplastid, Skin Diseases, Parasitic
RecruitingObservational study
Ex Vivo Immunogenicity Screening of Vaccine Candidate Antigen Combinations in Ethiopian Patients With Leishmaniasis
Leishmaniasis, Cutaneous, Leishmaniasis
RecruitingObservational study
LEISH-PED: Study on Leishmaniasis in Children
Leishmania Infantum Disease, Leishmaniasis, Visceral
RecruitingObservational study
Recurrent Visceral Leishmaniasis in HIV Co-Infection
Hiv, Visceral Leishmaniasis
Active, not recruitingObservational study
A Study to Assess Immune Response Status in Patients Before and After Treatment for Visceral Leishmaniasis
Visceral Leishmaniasis
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.
Carlos HN Costa, MD PhD principal investigator
Federal University of Piaui
Dorcas L Costa, MD PhD principal investigator
Federal University of Piaui
Ana LT Rabello, MD PhD principal investigator
Centro de Pesquisas Rene Rachou - Fiocruz - Minas Gerais
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Antimoniate of N-methylglucamine, amphotericin B deoxycholate and Liposomal amphotericin B in people with Visceral Leishmaniasis, run by University of Brasilia at 5 sites in Brazil.
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 5 inclusion and 11 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: stopped early, as of the sponsor's last update on 5 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Brazil. 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?
The study was stopped early (reason given: DSMB recommendation based on programmed interim analysis.). Results are not available in the source record.
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?
Cure rate (time frame: 6 month). 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 NCT01310738, 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 5 Sep 2017.