Visceral LeishmaniasisPhase 3NCT00696969
Safety and Efficacy Study to Evaluate Different Combination Treatment Regimens for Visceral Leishmaniasis
A Phase 3 study testing Amphotericin B Deoxycholate, Ambisome + Miltefosine and Ambisome and Paromomycin in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 2 sites in India.
Trial summary
The overall objective of this trial is to identify a safe and effective combination, (coadministration) short course treatment for the treatment of visceral leishmaniasis which could be easily deployed in a control programme and will reduce the risk of parasite resistance occurring. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Visceral Leishmaniasis
- What is being tested?
- Amphotericin B Deoxycholate, Ambisome + Miltefosine and Ambisome and Paromomycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 634 participants
- Where
- 2 sitesIndia
- Study dates
- Jun 2008to Jan 2010
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adults ( male or female) 18-60 years of age
- Acute, symptomatic, non-severe (minimum Hb.5 gm/dL) VL proven by parasitological examination of splenic or bone marrow aspirate.
- History of fever.
- Living within reachable distance of the trial site to enable attendance for follow-up visits
- Written informed consent to participate
- Proven HIV negative status
- Women of child-bearing potential who are using an assured method of contraception
Who cannot join
- Signs/symptoms indicative of severe VL ( Hb.< 5gm/dl, evidence of cardiac failure, etc)
- Patients who have received anti-leishmanial or anti-fungal treatment within the last 45 days
- Patients who have received any investigational (unlicensed) drugs within the last 6 months
- Severe malnutrition BMI<15 in adults, weight for height less than 60% in children.
- Chronic underlying disease such as severe cardiac, renal, or hepatic impairment.
- Renal function tests (serum creatinine) outside the normal range
Show all 20Show fewer
- Liver function tests (transaminases) more than three times the upper limit of the normal range at study entry
- Jaundice (bilirubin >2.0mg/dL)
- Known hepatitis B or C positive
- Platelet count less than 40,000/mm3
- Prothrombin time 5 seconds or greater than normal range
- TotalWBC < 1,000/mm3
- Known alcohol or other drug abuse
- HIV positive status
- Pregnancy and/or lactation
- Females having unprotected sexual intercourse, or using a non-assured method of contraception (e.g. condom)
- Concomitant chronic drug treatment eg for diabetes, hypertension, TB, HIV etc
- Concomitant drug usage for acute infection, eg malaria, pneumonia etc within the last 7 days
- Any other condition which may invalidate the trial
- Known hypersensitivity to AmBisome, Paromomycin, amphotericin B and/or Miltefosine
Trial locations and contacts
2 sites in 1 country.
India2 sites
Kala-azar medical centre
Muzaffarpur, Bihar
Rajendra Memorial research Institute
Patna, Bihar
About this study
Official title: Randomized, Open-label, Parallel-group, Safety & Efficacy Study to Evaluate Different Combination Treatment Regimens, of Either AmBisome and Paromomycin, AmBisome and Miltefosine, or Paromomycin and Miltefosine Compared With Amphotericin B Deoxycholate (the Standard) Therapy for the Treatment of Acute, Symptomatic Visceral Leishmaniasis (VL).
The overall objective of this trial is to identify a safe and effective combination, (coadministration) short course treatment for the treatment of visceral leishmaniasis which could be easily deployed in a control programme and will reduce the risk of parasite resistance occurring.
Safety and tolerability should be such that the combination can be easily deployed.
Read the detailed description
New, effective, less toxic and simplified treatments are urgently needed to replace or complement the few currently available drugs to treat visceral Leishmaniasis. An interim strategy and one which will slow the emergence of resistant parasite strains is to use coadministration of currently available drugs.
In India, first line treatment is now amphotericin B which is administered as an intravenous infusion, on alternate days over a 4 week period. A liposomal formulation of amphotericin B, AmBisome, is also available, and is substantially less nephrotoxic than amphotericin B, but is expensive.
It is acknowledged that AmBisome is the most effective therapy for visceral leishmaniasis, but it's high cost has hampered implementation. Use as part of a combination treatment, potentially as a single, lower dose, could reduce treatment costs considerably and thereby increase access for patients.
Two new treatments have recently been licensed in India for the treatment of patients with VL,
- Paromomycin administered as an intramuscular injection, once daily for 21 days
- Miltefosine administered as an oral tablet, once daily for 28 days. These drugs are now being used as monotherapy with high risk of emergence of resistant parasites. With price reduction for AmBisome, preferential pricing for Miltefosine and the concern for emergence of resistant parasites due to monotherapy, it is time to move rapidly toward obtaining definitive data for making recommendations on combination therapy as soon as possible, before these valuable drugs become useless. The present protocol will be a definitive Phase-III trial with the aim that at the end of this trial, strong evidence-based recommendations on combination therapy with available drugs can be made to Authorities in the Indian sub-continent. This protocol will evaluate various combinations of the three drugs; AmBisome, Paromomycin and Miltefosine at reduced total dosage and in shorter courses, against the present standard treatment with amphotericin B deoxycholate.
- Conditions
- Visceral Leishmaniasis
- Being tested
- Amphotericin B Deoxycholate, Ambisome + Miltefosine, Ambisome and Paromomycin, Miltefosine and Paromomycin
- Medical subject headings
- Leishmaniasis, Visceral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amphotericin B DeoxycholateDrug
1 mg/kg e.o.d for 30 days
Ambisome + MiltefosineDrug
Ambisome (i.v. single dose 5 mg/kg)+ Miltefosine 7 days
Ambisome and ParomomycinDrug
Ambisome 5 mg/kg single dose + Paromomycin Sulphate 15mg/kg/day for 10 days
Miltefosine and ParomomycinDrug
Miltefosine (standard dose) and Paromomycin Sulphate 15mg/kg/day for 10 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Not described Receives: Drug: Amphotericin B Deoxycholate |
| 2 | Experimental | Not described Receives: Drug: Ambisome + Miltefosine |
| 3 | Experimental | Not described Receives: Drug: Ambisome and Paromomycin |
| 4 | Experimental | Not described Receives: Drug: Miltefosine and Paromomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Definitive cure based on parasitological clearance at Day 15 after start of combination therapy (Day 31 for standard therapy), no evidence of parasites at day 45 and no clinical signs or symptoms of VL at 6 months post treatment.
Measured: 6 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2008 (estimated)
- Study startJun 2008
- Primary completionJan 2010
- Study completionJan 2010
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 634 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Investigators
- Farrokh Modabber, Study director, Drugs for Neglected Diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00696969
- Sponsor's protocol ID
- VL Combo 07
- Status last verified
- Feb 2010
- First submitted
- 11 Jun 2008
- Last updated
- 11 Feb 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sundar S, Sinha PK, Rai M, Verma DK, Nawin K, Alam S, Chakravarty J, Vaillant M, Verma N, Pandey K, Kumari P, Lal CS, Arora R, Sharma B, Ellis S, Strub-Wourgaft N, Balasegaram M, Olliaro P, Das P, Modabber F. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet. 2011 Feb 5;377(9764):477-86. doi: 10.1016/S0140-6736(10)62050-8. Epub 2011 Jan 20.
PubMed 21255828
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Open-label, Parallel-group, Safety & Efficacy Study to Evaluate Different Combination Treatment Regimens, of Either AmBisome and Paromomycin, AmBisome and Miltefosine, or Paromomycin and Miltefosine Compared With Amphotericin B Deoxycholate (the Standard) Therapy for the Treatment of Acute, Symptomatic Visceral Leishmaniasis (VL).
- ClinicalTrials.gov ID
- NCT00696969
- Acronym / sponsor ID
- VL Combo 07
- Conditions
- Visceral Leishmaniasis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 634 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 13 Jun 2008 (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.
The overall objective of this trial is to identify a safe and effective combination, (coadministration) short course treatment for the treatment of visceral leishmaniasis which could be easily deployed in a control programme and will reduce the risk of parasite resistance occurring.
Safety and tolerability should be such that the combination can be easily deployed.
Detailed description
New, effective, less toxic and simplified treatments are urgently needed to replace or complement the few currently available drugs to treat visceral Leishmaniasis. An interim strategy and one which will slow the emergence of resistant parasite strains is to use coadministration of currently available drugs.
In India, first line treatment is now amphotericin B which is administered as an intravenous infusion, on alternate days over a 4 week period. A liposomal formulation of amphotericin B, AmBisome, is also available, and is substantially less nephrotoxic than amphotericin B, but is expensive.
It is acknowledged that AmBisome is the most effective therapy for visceral leishmaniasis, but it's high cost has hampered implementation. Use as part of a combination treatment, potentially as a single, lower dose, could reduce treatment costs considerably and thereby increase access for patients.
Two new treatments have recently been licensed in India for the treatment of patients with VL,
- Paromomycin administered as an intramuscular injection, once daily for 21 days
- Miltefosine administered as an oral tablet, once daily for 28 days. These drugs are now being used as monotherapy with high risk of emergence of resistant parasites. With price reduction for AmBisome, preferential pricing for Miltefosine and the concern for emergence of resistant parasites due to monotherapy, it is time to move rapidly toward obtaining definitive data for making recommendations on combination therapy as soon as possible, before these valuable drugs become useless. The present protocol will be a definitive Phase-III trial with the aim that at the end of this trial, strong evidence-based recommendations on combination therapy with available drugs can be made to Authorities in the Indian sub-continent. This protocol will evaluate various combinations of the three drugs; AmBisome, Paromomycin and Miltefosine at reduced total dosage and in shorter courses, against the present standard treatment with amphotericin B deoxycholate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Amphotericin B Deoxycholate |
| 2 | Experimental | Drug: Ambisome + Miltefosine |
| 3 | Experimental | Drug: Ambisome and Paromomycin |
| 4 | Experimental | Drug: Miltefosine and Paromomycin |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Adults ( male or female) 18-60 years of age
- Acute, symptomatic, non-severe (minimum Hb.5 gm/dL) VL proven by parasitological examination of splenic or bone marrow aspirate.
- History of fever.
- Living within reachable distance of the trial site to enable attendance for follow-up visits
- Written informed consent to participate
Key exclusion criteria (20 listed)
- Signs/symptoms indicative of severe VL ( Hb.< 5gm/dl, evidence of cardiac failure, etc)
- Patients who have received anti-leishmanial or anti-fungal treatment within the last 45 days
- Patients who have received any investigational (unlicensed) drugs within the last 6 months
- Severe malnutrition BMI<15 in adults, weight for height less than 60% in children.
- Chronic underlying disease such as severe cardiac, renal, or hepatic impairment.
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 |
|---|---|---|
| Amphotericin B Deoxycholate1 mg/kg e.o.d for 30 days | Drug | 1 |
| Ambisome + MiltefosineAmbisome (i.v. single dose 5 mg/kg)+ Miltefosine 7 days | Drug | 2 |
| Ambisome and ParomomycinAmbisome 5 mg/kg single dose + Paromomycin Sulphate 15mg/kg/day for 10 days | Drug | 3 |
| Miltefosine and ParomomycinMiltefosine (standard dose) and Paromomycin Sulphate 15mg/kg/day for 10 days | Drug | 4 |
Primary outcome
Definitive cure based on parasitological clearance at Day 15 after start of combination therapy (Day 31 for standard therapy), no evidence of parasites at day 45 and no clinical signs or symptoms of VL at 6 months post treatment.
Time frame: 6 months post treatment
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 11 Feb 2010.
- Derived from this study: PubMed 21255828Sundar S, Sinha PK, Rai M, Verma DK, Nawin K, Alam S, Chakravarty J, Vaillant M, Verma N, Pandey K, Kumari P, Lal CS, Arora R, Sharma B, Ellis S, Strub-Wourgaft N, Balasegaram M, Olliaro P, Das P, Modabber F. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet. 2011 Feb 5;377(9764):477-86. doi: 10.1016/S0140-6736(10)62050-8. Epub 2011 Jan 20.
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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.
Farrokh Modabber study director
Drugs for Neglected Diseases
2 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 Amphotericin B Deoxycholate, Ambisome + Miltefosine and Ambisome and Paromomycin in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 2 sites in India.
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 7 inclusion and 20 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 11 Feb 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in India. 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?
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?
Definitive cure based on parasitological clearance at Day 15 after start of combination therapy (Day 31 for standard therapy), no evidence of parasites at day 45 and no clinical signs or symptoms of VL at 6 months post treatment. (time frame: 6 months post treatment). 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 NCT00696969, 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 11 Feb 2010.