Trial Outcomes & Findings for Efficacy and Safety of Miltefosine or Thermotherapy for Cutaneous Leishmaniasis in Colombia. (NCT NCT00471705)

NCT ID: NCT00471705

Last Updated: 2019-01-16

Results Overview

Complete Clinical response: Initial cure plus the absence of recurrences or mucosal lesions for 6 months after the end of treatment. Note: nitial cure: Complete re-epithelialization of all ulcers and complete disappearance of the induration up to 3 months after the end of treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 437 participants
• Primary outcome timeframe: Until 6 months posttreatment
• Results posted on: 2019-01-16

Participant Flow

The study was carried out between June 2006 and April 2008. The subjects of the study were adult males serving in the Colombian Army. The study was carried out in five military health establishments located in central, northeast and southern Colombia.

Screening was performed to 486 volunteers, of whom 49 were excluded for several reasons, as follows: Failure to meet inclusion criteria (n=12), unwillingness to participate (n=14) and completion of military service within 6 months (n=23)

Participant milestones

Measure	Miltefosine Miltefosine 2.5 mg/Kg/day with a maximum dose of 150 mg PO day.	Glucantime® Glucantime® 20 mg /Kg /day for 20 days (intramuscular)	Thermotherapy One session of local heat using a thermotherapy device at 50 celsius degrees during 30 seconds.
Overall Study STARTED	145	143	149
Overall Study COMPLETED	121	121	134
Overall Study NOT COMPLETED	24	22	15

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of Miltefosine or Thermotherapy for Cutaneous Leishmaniasis in Colombia.

Baseline characteristics by cohort

Measure	Miltefosine n=145 Participants Miltefosine 2.5 mg/Kg/day with a maximum dose of 150 mg PO day.	Glucantime® n=143 Participants Glucantime® 20 mg /Kg /day for 20 days (intramuscular)	Thermotherapy n=149 Participants One session of local heat using a thermotherapy device at 50 celsius degrees during 30 seconds.	Total n=437 Participants Total of all reporting groups
Age, Continuous	23 years n=93 Participants	23 years n=4 Participants	23 years n=27 Participants	23 years n=483 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Sex: Female, Male Male	145 Participants n=93 Participants	143 Participants n=4 Participants	149 Participants n=27 Participants	437 Participants n=483 Participants
Region of Enrollment Colombia	145 participants n=93 Participants	143 participants n=4 Participants	149 participants n=27 Participants	437 participants n=483 Participants

PRIMARY outcome

Timeframe: Until 6 months posttreatment

Population: The efficacy of the treatments was calculated by intention to treat and by protocol.

Complete Clinical response: Initial cure plus the absence of recurrences or mucosal lesions for 6 months after the end of treatment.

Note: nitial cure: Complete re-epithelialization of all ulcers and complete disappearance of the induration up to 3 months after the end of treatment.

Outcome measures

Measure	Miltefosine n=145 Participants Miltefosine 2.5 mg/Kg/day with a maximum dose of 150 mg PO day.	Glucantime® n=143 Participants Glucantime® 20 mg /Kg /day for 20 days (intramuscular)	Thermotherapy n=149 Participants One session of local heat using a thermotherapy device at 50 celsius degrees during 30 seconds.
Complete Clinical Response	85 participants	103 participants	86 participants

PRIMARY outcome

Timeframe: Until 3 months posttreatment

At least 50% increase in lesion size at the end of treatment, absence of clinical response at 6 weeks, or any sign of lesion activity 3 months after the end of treatment

Outcome measures

Measure	Miltefosine n=145 Participants Miltefosine 2.5 mg/Kg/day with a maximum dose of 150 mg PO day.	Glucantime® n=143 Participants Glucantime® 20 mg /Kg /day for 20 days (intramuscular)	Thermotherapy n=149 Participants One session of local heat using a thermotherapy device at 50 celsius degrees during 30 seconds.
Failure	34 participants	14 participants	42 participants

SECONDARY outcome

Timeframe: Until 6 months post-treatment

Reactivation of the lesion at the original site after cure or mucosal compromise during follow-up.

Outcome measures

Measure	Miltefosine n=145 Participants Miltefosine 2.5 mg/Kg/day with a maximum dose of 150 mg PO day.	Glucantime® n=143 Participants Glucantime® 20 mg /Kg /day for 20 days (intramuscular)	Thermotherapy n=149 Participants One session of local heat using a thermotherapy device at 50 celsius degrees during 30 seconds.
Recurrence	3 Participants	4 Participants	6 Participants

Adverse Events

Miltefosine

Serious events: 1 serious events

Other events: 125 other events

Deaths: 0 deaths

Glucantime®

Serious events: 3 serious events

Other events: 121 other events

Deaths: 0 deaths

Thermotherapy

Serious events: 0 serious events

Other events: 110 other events

Deaths: 0 deaths

Serious adverse events

Measure	Miltefosine n=145 participants at risk Miltefosine 2.5 mg/Kg/day with a maximum dose of 150 mg PO day.	Glucantime® n=143 participants at risk Glucantime® 20 mg /Kg /day for 20 days (intramuscular)	Thermotherapy n=149 participants at risk One session of local heat using a thermotherapy device at 50 celsius degrees during 30 seconds.
Social circumstances Death in combat	0.00% 0/145 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	1.4% 2/143 • Number of events 2 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	0.00% 0/149 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Social circumstances Stab wound	0.00% 0/145 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	0.70% 1/143 • Number of events 1 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	0.00% 0/149 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Gastrointestinal disorders Hematemesis	0.69% 1/145 • Number of events 1 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	0.00% 0/143 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	0.00% 0/149 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.

Other adverse events

Measure	Miltefosine n=145 participants at risk Miltefosine 2.5 mg/Kg/day with a maximum dose of 150 mg PO day.	Glucantime® n=143 participants at risk Glucantime® 20 mg /Kg /day for 20 days (intramuscular)	Thermotherapy n=149 participants at risk One session of local heat using a thermotherapy device at 50 celsius degrees during 30 seconds.
General disorders Fever (Middle of treatment)	6.2% 8/130 • Number of events 8 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	9.2% 11/119 • Number of events 11 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	3.2% 4/124 • Number of events 4 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Musculoskeletal and connective tissue disorders Myalgia (Middle of treatment)	6.9% 9/130 • Number of events 9 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	10.1% 12/119 • Number of events 12 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	2.4% 3/124 • Number of events 3 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Musculoskeletal and connective tissue disorders Arthralgia (Middle of treatment)	6.9% 9/130 • Number of events 9 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	14.3% 17/119 • Number of events 17 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	2.4% 3/124 • Number of events 3 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
General disorders Cephalea (Middle of treatment)	17.7% 23/130 • Number of events 23 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	14.3% 17/119 • Number of events 17 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	8.1% 10/124 • Number of events 10 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Gastrointestinal disorders Vomiting (Middle of treatment)	22.3% 29/130 • Number of events 29 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	2.5% 3/119 • Number of events 3 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	2.4% 3/124 • Number of events 3 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Gastrointestinal disorders Nausea (Middle of treatment)	29.2% 38/130 • Number of events 38 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	3.4% 4/119 • Number of events 4 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	4.0% 5/124 • Number of events 5 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Gastrointestinal disorders Anorexia (Middle of treatment)	14.6% 19/130 • Number of events 19 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	6.7% 8/119 • Number of events 8 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	4.0% 5/124 • Number of events 5 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Renal and urinary disorders BUN (Middle of treatment)	0.00% 0/94 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	4.0% 4/99 • Number of events 4 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	1.0% 1/96 • Number of events 1 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Hepatobiliary disorders ALT (Middle of treatment)	12.9% 17/132 • Number of events 17 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	13.9% 19/137 • Number of events 19 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	7.5% 8/106 • Number of events 8 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Hepatobiliary disorders Amylase (Middle of treatment)	25.9% 29/112 • Number of events 29 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	13.5% 15/111 • Number of events 15 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	6.9% 6/87 • Number of events 6 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
General disorders Fever (End of treatment)	6.2% 8/129 • Number of events 8 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	22.1% 29/131 • Number of events 29 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	3.0% 4/132 • Number of events 4 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Musculoskeletal and connective tissue disorders Myalgia (End of treatment)	12.4% 16/129 • Number of events 16 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	51.1% 67/131 • Number of events 67 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	3.0% 4/132 • Number of events 4 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Musculoskeletal and connective tissue disorders Arthralgia (End of treatment)	10.1% 13/129 • Number of events 13 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	49.6% 65/131 • Number of events 65 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	2.3% 3/132 • Number of events 3 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
General disorders Cephalea (End of treatment)	23.3% 30/129 • Number of events 30 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	39.7% 52/131 • Number of events 52 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	9.8% 13/132 • Number of events 13 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Gastrointestinal disorders Vomiting (End of treatment)	34.1% 44/129 • Number of events 44 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	12.2% 16/131 • Number of events 16 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	1.5% 2/132 • Number of events 2 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Gastrointestinal disorders Nausea (End of treatment )	45.7% 59/129 • Number of events 59 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	20.6% 27/131 • Number of events 27 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	3.0% 4/132 • Number of events 4 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Gastrointestinal disorders Anorexia (End of treatment )	28.7% 37/129 • Number of events 37 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	34.4% 45/131 • Number of events 45 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	4.5% 6/132 • Number of events 6 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Gastrointestinal disorders Diarrhea (End of treatment)	4.7% 6/129 • Number of events 6 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	1.5% 2/131 • Number of events 2 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	0.76% 1/132 • Number of events 1 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Gastrointestinal disorders Abdominal Pain (End of treatment)	7.0% 9/129 • Number of events 9 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	1.5% 2/131 • Number of events 2 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	0.00% 0/132 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Renal and urinary disorders BUN (End of treatment)	2.9% 3/102 • Number of events 3 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	0.88% 1/114 • Number of events 1 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	2.6% 2/78 • Number of events 2 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Hepatobiliary disorders AST (End of treatment)	4.9% 5/103 • Number of events 5 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	9.9% 11/111 • Number of events 11 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	2.7% 2/75 • Number of events 2 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Hepatobiliary disorders ALT (End of treatment)	16.3% 15/92 • Number of events 15 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	12.2% 11/90 • Number of events 11 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	11.4% 12/105 • Number of events 12 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Hepatobiliary disorders Amylase (End of treatment )	10.2% 11/108 • Number of events 11 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	22.0% 24/109 • Number of events 24 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	10.0% 7/70 • Number of events 7 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Blood and lymphatic system disorders Haemoglobin (End of treatment)	1.0% 1/98 • Number of events 1 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	6.5% 7/108 • Number of events 7 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	2.9% 2/70 • Number of events 2 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Renal and urinary disorders Creatinine (middle of treatment)	6.7% 8/120 • Number of events 8 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	10.7% 12/112 • Number of events 12 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	8.0% 7/87 • Number of events 7 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Renal and urinary disorders Creatinine (end of treatment)	6.1% 6/99 • Number of events 6 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	0.87% 1/115 • Number of events 1 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	1.2% 1/81 • Number of events 1 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Skin and subcutaneous tissue disorders Lesion pain (middle of treatment)	10.8% 14/130 • Number of events 14 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	2.5% 3/119 • Number of events 3 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	21.8% 27/124 • Number of events 27 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Skin and subcutaneous tissue disorders Lesion infection (middle of treatment)	3.8% 5/130 • Number of events 5 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	1.7% 2/119 • Number of events 2 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	7.3% 9/124 • Number of events 9 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Hepatobiliary disorders AST (Middle of treatment)	7.6% 8/105 • Number of events 8 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	8.1% 8/99 • Number of events 8 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	11.8% 11/93 • Number of events 11 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Blood and lymphatic system disorders Haemoglobin (middle of treatment	4.4% 5/113 • Number of events 5 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	4.7% 5/107 • Number of events 5 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	5.2% 5/96 • Number of events 5 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.
Skin and subcutaneous tissue disorders Lesion pain (end of treatment)	8.5% 11/129 • Number of events 11 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	12.2% 16/131 • Number of events 16 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.	14.8% 18/122 • Number of events 18 • During treatment and 6 months after treatment The Risk population differs across Adverse Events terms because not all lab tests were available at all study sites.

Additional Information

Iván Darío Vélez Bernal

Universidad de Antioquia - Colombia

Phone: 574 + 219 6501 - 02

Email: idvelez@pecet-colombia.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place