Assessing three day pentamidine for first stage human african trypanosomiasis in Uganda

ISRCTN	ISRCTN55042030
DOI	https://doi.org/10.1186/ISRCTN55042030
Secondary identifying numbers	A60914; HAT PDE 06-02

Submission date: 14/12/2007
Registration date: 14/12/2007
Last edited: 18/02/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Deborah Kioy
Scientific

World Health Organization
20 Avenue Appia
Geneva-27
CH-1211
Switzerland

Phone	+41 (0)22 791 3524
Email	kioyd@who.int

Study information

Study design	Non-inferiority clinical trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Assessing three day pentamidine for first stage human african trypanosomiasis in Uganda
Study objectives	Human African Trypanosomiasis (HAT) occurs in two forms, a generally acute form caused by Trypanosoma brucei rhodesiense and a usually chronic form caused by Trypanosoma brucei gambiense. Its epidemiology is dependent upon conducive environmental factors and the interaction between humans, tsetse flies (glossina) and trypanosomes. The control accordingly involves action on the reservoir and the vector; the specifics though differ for the two forms. For the case of T. b. gambiense, the action on the reservoir (mainly the human host) involves case detection (passively or actively) and chemotherapy with antitrypanosomal agents along with supportive treatment. The current treatment of stage I (also called early or haemolymphatic stage) T.b. gambiense HAT consists of 7 - 10 daily intramuscular injections of pentamidine 4 mg/kg. Pharmacokinetics studies have shown that pentamidine has a large volume of distribution and elimination occurs over weeks via metabolism, thus allowing the drug to remain in the body over long periods. The currently used regimen for pentamidine in sleeping sickness patients was derived before such pharmacokinetic data were available. With regimen of 7 - 10 days pentamidine intramuscular (IM) (4 mg/kg) currently used in stage I sleeping sickness, pentamidine accumulation occurs to a significant degree. Unsurprisingly, systemic side-effects such as hypoglycaemia are reported to be more common after the first week of such therapy The objective of the study is to compare the efficacy of 3 days IM pentamidine with the standard 7 day IM regimen (both at 4 mg/kg/day). Please note that the pilot study for this trial was held in Angola and was registered under the following details: Title: Assessing three day pentamidine for early stage human African trypanosomiasis (Angola) Registration reference: ISRCTN35617647 (see http://www.controlled-trials.com/ISRCTN35617647)
Ethics approval(s)	Ethics approval received from: 1. Ethical Clearance Committee (Uganda) on the 8th December 2006 (ref: VCD/UNCT 08 12 06) 2. World Health Organization (WHO) Ethics Review Committee (ERC) on the 18th July 2007 (ref: A60914)
Health condition(s) or problem(s) studied	Human African Trypanosomiasis (HAT)
Intervention	1. Three days pentamidine IM at a dose of 4 mg/kg/day 2. Seven days pentamidine IM at a dose of 4 mg/kg/day Contact details for Principal Investigator: Dr Jimmy Opigo District Directorate of Health Services Moyo District Local Government P.O. Box 1 Moyo, Uganda Tel: +256 (0)37 2273721 Moblie: +256 (0)77 2962601 Email: opigojimmy@gmail.com
Intervention type	Other
Primary outcome measure	Proportion of cases with favourable evolution at 6 months post-treatment, based on laboratory results.
Secondary outcome measures	1. Proportion of cases with favourable evolution at the end of treatment assessment (day 10), 3 and 12 months post-treatment, based on laboratory results 2. Cure rate at 18 months post-treatment, based on laboratory results 3. Frequency and severity of adverse events
Overall study start date	01/12/2007
Completion date	30/06/2011

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Both
Target number of participants	440
Key inclusion criteria	1. Age greater than or equal to 10 years and less than 60 years 2. Trypanosome positive lymph node aspirate or blood 3. Consenting patient 4. Alternative diagnoses excluded by appropriate clinical and laboratory investigations
Key exclusion criteria	1. Abnormal Cerebrospinal Fluid (CSF): 1.1. CSF White Blood Cell [WBC] count greater than 5 WBC/µl 1.2. Presence of trypanosomes 1.3. Haemorrhagic CSF 2. Pregnant 3. Previous HAT treatment 4. Known allergy or reaction to pentamidine 5. Diabetes mellitus 6. Severe difficulty expected with follow-up. Follow-up is difficult for all patients; only if it appears very probable that a patient will not be able to present for follow-up examinations until 18 months post-treatment should he/she be excluded (e.g. Sudanese refugees who have enrolled in the ongoing voluntary repatriation programme) 7. Patients with severe chronic conditions for whom the chance of survival until the end of the 18 months follow-up period is doubtful (e.g. clinical Human Immunodeficiency Virus [HIV]/Acquired Immune Deficiency Syndrome [AIDS] stage IV and Tuberculosis)
Date of first enrolment	01/12/2007
Date of final enrolment	30/06/2011

Locations

Countries of recruitment

Switzerland
Uganda

Study participating centre

World Health Organization

Geneva-27
CH-1211
Switzerland

Sponsor information

UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR)
Research organisation

20, Avenue Appia
Geneva-27
CH-1211
Switzerland

Phone	+41 (0)22 791 3524
Email	tdr@who.int
Website	http://who.int/tdr
"ROR"	https://ror.org/01f80g185

Funders

Funder type

Research organisation

United Nations Children's Fund (UNICEF)/United Nations Development Programme (UNDP)/World Bank/World Health Organization (WHO) - Special Programme for Research and Training in Tropical Diseases (TDR)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	04/07/2009	18/02/2021	Yes	No

Editorial Notes

18/02/2021: Publication reference added.