Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) Versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic Filariasis
Phase: NA
Conditions: Lymphatic Filariasis
Sponsor: Washington University School of Medicine

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“Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for 
Lymphatic Filariasis in Haiti” 
Protocol Identifier: DOLF_IDA_Haiti 
Type: Community-Based Mass Drug Administration 
Funding Sources:  This project is funded by the Bill and Melinda Gates Foundation through the 
Death for Onchocerciasis and Lymphatic Filariasis Project (DOLF), Washington University in St. 
Louis.  
 
Project Principal Investigator(s): Gary Weil, MD, Washington University, USA 
Christopher King, MD, PhD, MPH, Case Western Reserve University, USA 
Principal Investigator for MSPP: Jean Frantz Lemoine, MD, MPH 
Ministère de la Santé Publique et de la Population (MSPP), Haïti 
Principal Investigator for CDC: Christine Dubray, MD, MSc 
Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA 
CDC Co-Investigators: LeAnne Fox, MD, MPH; Anita Sircar, MD, MPH; Kimberly Won; Ryan 
Wiegand, PhD 
Non-CDC Co-Investigators: Valery D. Madsen Beau de Rochars, MD, MPH ; University of 
Florida (UF); Abdel N. Direny, MD, MPH; RTI International (RTI); Carl Renand Fayette, MD; 
IMA World Health (IMA), Port au Prince, Haiti and Washington, DC 
Initial Protocol:  v.1.0 
24 March 2016 
Amendment 1:   v.2.0 
22 May 2016 
Amendment 2: v.2.1   
22 August 2016 
Amendment 3: v.2.2   
05 July 2017 

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INVESTIGATOR AGREEMENT 
“Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for 
Lymphatic Filariasis in Haiti” 
DOLF_IDA_Haiti: v2.2   05 July 2017  
I have read the protocol, including the appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described.  I will conduct this study as 
outlined and make a reasonable effort to complete the study within the time designated. 
 
 
I will provide all study personnel, participating in the study under my supervision copies of the 
protocol and access to all study related information provided by the DOLF project.  I will discuss 
with them to ensure they are full informed about the study drug(s) and the study procedures. 
 
 
 
 
 
 
Principle Investigator: ___________________________________________    
 
                    Name/Title  (Print/Type) 
 
Signed:  
Date: 
 
NOTE:  Both the Project PI and local PI should have signed investigator agreements on file.   

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TABLE OF CONTENTS 
INVESTIGATOR AGREEMENT ...................................................................................... 2 
TABLE OF CONTENTS .................................................................................................. 3 
PRINCIPAUX ROLES ET RESPONSABILITÉES ........................................................... 6 
LIST OF ABBREVIATIONS ............................................................................................. 8 
1 PROTOCOL SUMMARY ........................................................................................... 9 
2 BACKGROUND INFORMATION AND RATIONALE ............................................... 13 
2.1 
General Context ...................................................................................................... 13 
2.2 
Country Specific Background ................................................................................... 13 
3 POTENTIAL RISKS AND BENEFITS ...................................................................... 16 
3.1 
Risks of Blood Draw ................................................................................................ 16 
3.2 
Risks of Study Drugs ............................................................................................... 16 
3.3 
Potential Participant and Community Benefit ........................................................... 16 
3.4 
Participant Participation and Cost ............................................................................ 17 
3.5 
Compensation for Injury ........................................................................................... 17 
4 STUDY DESIGN AND OBJECTIVES ...................................................................... 17 
4.1 
Study Objectives ...................................................................................................... 17 
4.1.1 Primary objective ....................................................................................... 17 
4.1.2 Secondary Objectives ............................................................................... 17 
4.2 
Study Design ........................................................................................................... 18 
4.3 
Study Screening and Enrollment ............................................................................. 18 
4.4 
Study Sites .............................................................................................................. 18 
4.5 
Preparatory Activities ............................................................................................... 18 
4.5.1 Social Mobilization..................................................................................... 18 
4.5.2 Household Enumeration, Census and Geo-Referencing ........................... 19 
4.6 
Pre-Treatment Assessment Team ........................................................................... 19 
4.6.1 Inclusion and Exclusion Criteria................................................................. 19 
4.6.2 Pregnant Females ..................................................................................... 20 
4.6.3 Informed Consent ...................................................................................... 20 
4.6.4 Baseline Survey ........................................................................................ 20 
4.6.5 Screening for Filarial Antigenemia and Microfilaria .................................... 21 
4.6.6 Randomization .......................................................................................... 21 
4.7 
Withdrawal ............................................................................................................... 21 
4.8 
Efficacy and Effectiveness of IDA vs DA .................................................................. 21 
4.9 
Retreatment ............................................................................................................. 22 
4.10 
Guidelines for Stopping the Trial ............................................................................ 22 
4.11 
Triple Drug Regimen Acceptability ......................................................................... 22 
5 INVESTIGATIONAL PRODUCT .............................................................................. 24 
5.1 
Study Drug Background ........................................................................................... 24 
5.2 
Product Supply and Storage .................................................................................... 25 

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5.3 
Triple Drug Therapy (IDA) and Two-Drug Therapy (DA) .......................................... 25 
6 SAFETY REPORTING AND SAFETY MONITORING ............................................. 25 
6.1 
Definitions ................................................................................................................ 25 
6.2 
Assessment of Adverse Events ............................................................................... 26 
6.3 
Serious Adverse Event (SAE) Assessment and Management ................................. 27 
6.4 
Reporting of Pregnancy ........................................................................................... 27 
6.5 
Safety Monitoring by the Oversight Committee ........................................................ 27 
6.6 
Country Specific Safety Reporting ........................................................................... 28 
7 CLINICAL MANAGEMENT OF EVENTS ................................................................. 28 
7.1 
Adverse Event Monitoring and Management ........................................................... 28 
7.1.1 Mild Localized Symptoms .......................................................................... 28 
7.1.2 Moderate to Severe Localized Adverse Events ......................................... 29 
7.1.3 Moderate Systematic Adverse Events ....................................................... 29 
7.1.4 Moderate to Severe Systemic Adverse Events .......................................... 29 
7.2 
Rapid Response Teams for Management of Adverse Events .................................. 29 
8 STATISTICAL CONSIDERATIONS ......................................................................... 29 
8.1 
Safety ...................................................................................................................... 29 
8.2 
Efficacy .................................................................................................................... 30 
8.3 
Enrolling Additional Participants .............................................................................. 30 
9 DATA HANDLING/RECORD KEEPING/SOURCE DOCUMENTS .......................... 31 
9.1 
Types of Data Collected .......................................................................................... 31 
9.2 
Study Records Retention ......................................................................................... 32 
9.3 
Source Documents .................................................................................................. 32 
10 RESPONSIBILITIES .............................................................................................. 32 
10.1 
Investigator Responsibilities .................................................................................. 32 
10.2 
Good Clinical Practice ........................................................................................... 32 
10.3 
Institutional Review Board (IRB)/Ethics Committee (EC) ....................................... 32 
10.4 
Informed Consent .................................................................................................. 33 
10.4.1 Informed Consent Training ........................................................................ 33 
10.4.2 Country Specific ICF Information ............................................................... 33 
10.5 
Participant Privacy ................................................................................................. 34 
10.6 
Data Ownership ..................................................................................................... 34 
11 PUBLICATION POLICY ......................................................................................... 35 
12 LITERATURE  REFERENCES .............................................................................. 36 
13 LIST OF APPENDICES ......................................................................................... 37 
Appendix 1: 
Study Flow Diagram (Country Specific) ........................................... 38 
Appendix 2: 
Participant Enrollment Form [Example] ........................................... 39 
Appendix 3: 
Participant Monitoring Form [Example] ............................................ 42 
Appendix 4:  
Guide to Assigning Adverse Event Severity..................................... 45 
Appendix 5: 
Adverse Event Evaluation and Report Form (AEERF) [Example] .... 48 
Appendix 5a: 
Required Reporting Guideline For Serious Adverse Events ............ 52 
Appendix 6A: 
Information Sheet and Informed Consent Form (version 1.2, 22 
August 20116) ....................................................................................................... 56 

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APPENDIX 6B: 
Informed re-Consent Form (V.1, 30 may 2017) ............................... 65 
 
 
 

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PRINCIPAUX ROLES ET RESPONSABILITÉES 
Principal Investigator for 
MSSP: 
 
Jean Frantz Lemoine, MD, MPH  
Programme National de la Malaria et de la Filariose Lymphatique 
(PNCM) 
Ministère de la Santé Publique et de la Population (MSPP) 
Address: Rue Monseigneur Guilloux,  
Palais des Ministères, Port-au-Prince, Haïti.  
Phone number: +1 (509) 3744-8755 or +1 (509) 3946-3026)  
Email: tileum@hotmail.com 
Principal Investigator for 
CDC: 
 
Christine Dubray, MD, MSc  
Division of Parasitic Diseases and Malaria, CDC 
Address: 1600 Clifton Road, MS A-06  
Atlanta, GA 30317, USA  
Phone number: +1(404)718-4769  
Email: ffg5@cdc.gov  
Co-Investigators: 
LeAnne Fox, MD, CDC  
Phone number: +1(404)718-4739  
Email: llf4@cdc.gov  
Anita Sircar, MD, MPH, CDC  
Phone number: +1(404)718-4728  
Email: yxi6@cdc.gov  
Kimberly Won, CDC  
Phone number: +1(404)718-4137  
Email: kfw7@cdc.gov 
Madsen Beau de Rochars, MD, MPH  
Emerging Pathogens Institute, University of Florida  
Phone number: (352) 294-5695  
Fax: (352) 273-9430  
Email: madsenbeau@phhp.ufl.edu 
Abdel N. Direny, MD, MPH, RTI  
Phone number: +1 (202) 974-7814  
Email: adireny@rti.org   
Carl Renand Fayette, MD, IMA 
Protocol Statistician: 
Ryan Wiegand, PhD, CDC  
Phone number: +1(404)639-2031  
Email: fwk2@cdc.gov  
 
Roles and Responsibilities of Partners: 
 
MSPP: MSPP is responsible for developing the protocol, submitting the protocol to the 
National Ethical Committee in Haiti, training study personnel on study methodology, 

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including individuals in the study, collecting, managing and analysing data, and preparing 
manuscript and abstract.  
 
CDC: CDC will provide technical assistance to MSPP, train study personnel on study 
methodology, and assist with data analysis and manuscript preparation. CDC personnel will 
not intervene or interact with living individuals included in the study or have access to 
personally identifiable information for research purposes.  
 UF and RTI: UF and RTI personnel will act as consultants to provide technical assistance to 
MSPP to assist with training of study personnel, appropriate implementation of standard 
operating procedure during the study, analysis of data, and preparation of manuscript. 
 IMA: IMA will act as the implementing partner for MSPP and will assist with study logistics, 
finance, hiring study personnel, and organization of trainings.  
 
 

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LIST OF ABBREVIATIONS 
GENERAL PROJECT ABBREVIATIONS 
 
AE 
Adverse Event/Adverse Experience 
AEERF 
Adverse Event Evaluation and Report Form 
ALB 
Albendazole 
CDC 
Centers for Disease and Control and Prevention 
CDD 
Community Drug Distributor 
CRF 
Case Report Form  
DA 
Two Drug Therapy (dyethilcarbamzine and albendazole)  
DEC 
Diethylcarbamazine 
DOLF 
Death for Onchocerciasis and Lymphatic Filariasis 
DOT 
Directly Observed Treatment 
DSMB, DSRB or DMC 
Data and Safety Monitoring Board also called Data Safety Review Board 
or  Data Monitoring Committee 
EC 
Ethics Committee (may also be called IRB or Institutional Review Board) 
EDC 
Electronic Data Capture 
FTS 
Filariasis Test Strip 
GCP 
Good Clinical Practice 
GPELF 
Global Programme to Eliminate Lymphatic Filariasis 
GPS 
Global Positioning System 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICT 
Immunochromatographic Test 
IDA 
Triple Drug Therapy (Ivermectin, Diethylcarbamazine, and Albendazole) 
IMA 
IMA World Health 

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IRB 
Institutional Review Board (may also be called EC) 
IVM 
Ivermectin 
LF 
Lymphatic Filariasis 
MDA 
Mass Drug Administration 
MF 
Microfilaria(e) 
Mg 
Milligram 
NTD 
Neglected Tropical Diseases 
NLM 
National Library of Medicine 
PI 
Principal Investigator 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
TAS 
Transmission Assessment Surveys 
UNID 
Unique Study Identification Numbers 
USAID 
United States Agency for International Development 
WHO 
World Health Organization 
COUNTRY SPECIFIC ABBREVIATIONS 
MSPP 
Ministère de la Santé Publique et de la Population 
1 PROTOCOL SUMMARY 
Study Title: 
Community Based Safety Study of 2-drug (Diethylcarbamazine and 
Albendazole) versus 3-drug (Ivermectin, Diethylcarbamazine and 
Albendazole) Therapy for Lymphatic Filariasis in Haiti 
Type of Study: 
Mass Drug Administration 
Population: 
IDA/ Triple Drug Arm: participants more than or equal to 5 years of 
age 
DA/ Dual Drug Arm (DA): participants more than or equal to 5 

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years of age 
Number of Treated 
Areas: 
Commune of Quartier Morin 
Duration of Study 
Participant 
Participation: 
Single treatment with daily adverse event follow-up thru Day 7, 
then a long-term follow-up at 1 year.   
Study Drugs 
Ivermectin (3 mg tablets)  *not included in two arm treatment 
Diethylcarbamazine (100 mg tablets) 
Albendazole (400 mg tablets) 
Primary Objectives: 
Determine the frequency, type, and severity of adverse events 
following triple drug therapy (IVM+DEC+ALB) compared to the 
standard two drug treatment (DEC+ALB) in infected and uninfected 
individuals in a community 
Secondary Objectives: 
 
Compare the efficacy of IDA (3 drug therapy) to DA (2 drug 
therapy) administered in communities for clearance of MF and 
filarial antigenemia 
Assess the effect of intensity of filarial infection on the frequency 
and severity of adverse events 
Compare community acceptance of Mass Drug Administration with 
three drug vs two drug therapy  
DOLF Project 
Integration 
This protocol is specific to Haiti, but the results will also be included 
in the larger inter-country DOLF project.  Data will be 
available/reviewed at a country level and at the project level.  
 
In 2000, the World Health Organization (WHO) launched the Global Programme to Eliminate 
Lymphatic Filariasis (GPELF) to eliminate lymphatic filariasis as a public health problem by 2020. 
To interrupt transmission, WHO recommends therapy using combinations of two medicines 
delivered to entire at risk populations through a strategy known as mass drug administration. 
Ivermectin and albendazole are administered in areas where onchocerciasis is co-endemic; 
diethylcarbamazine and albendazole are administered in areas where onchocerciasis is not co-
endemic. 
 

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Results of a pilot study in Papua New Guinea suggest that triple drug therapy (ivermectin, 
diethylcarbamazine and albendazole) is superior to the currently recommended two-drug 
regimen. A single dose of the triple therapy rapidly achieved complete clearance of Wuchereria 
bancrofti microfilariae from the blood of 12 individuals for at least one year post-treatment. All 
six individuals tested at 24 months were still amicrofilaremic, suggesting that the triple therapy 
might permanently sterilizes adult filarial worms. Many people treated in these studies 
experienced transient systemic adverse events commonly associated with diethylcarbamazine 
or ivermectin treatment of filariasis. Adverse events were more frequent after the triple 
therapy than after the usual combination of two drugs. However, no serious adverse events 
were observed. The dramatic reduction and sustained decrease of microfilaria along with the 
safety profile seen in the Papua New Guinea studies suggest that the triple drug therapy may be 
a useful tool to achieve the goal of eliminating lymphatic filariasis as a public health problem by 
2020.  
 
Although the study cited above has clearly demonstrated the superiority of the triple therapy 
for clearing W. bancrofti microfilaria from the blood, more safety and efficacy data are needed 
before triple therapy can be rolled out on a large scale as a mass drug administration regimen 
in lymphatic filariasis endemic countries. WHO recommends a best practice called “cohort 
event monitoring” for demonstrating safety of new drug regimens for public health program 
use. Establishing safety through such methodology requires pre and post treatment assessment 
from at least 10,000 people treated with the triple therapy across multiple settings.  
 
It is therefore proposed to conduct a cohort event monitoring study to acquire safety data in 
Haiti (Quartier Morin Commune). Efficacy and acceptability components will also be included in 
the study. Similar studies will be conducted simultaneously in India, Indonesia, Papua New 
Guinea, Fiji and Sri Lanka to reach the 10,000 people necessary to assess the safety of this new 
drug combination.  
 
 

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STUDY DESIGN 
General Flow Diagram: 
 
DOLF_IDA_Haiti Study 
ARM 1 
Sample Size: 3000 
Triple Drug 
ARM 2 
Sample Size: 3000 
Two Drug 
NOTE: A Study Flow Diagram specific for Haiti is provided in Appendix 1. 
  
 
Community Teams: 
Consent and Screen 
 
 
Review 
Eligibility 
Triple Drug 
(IDA) 
Two Drug 
(DA) 
FTS, MF Survey, Study Drug Administration 
  
Clinical and AE Assessment 
Data Entered into 
EDC 

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2 BACKGROUND INFORMATION AND RATIONALE 
2.1 General Context 
In 2000, the World Health Organization (WHO) launched the Global Programme to Eliminate 
Lymphatic Filariasis (GPELF) to eliminate lymphatic filariasis as a public health problem by 
2020 [1] To interrupt transmission, WHO recommends therapy using combinations of two 
medicines delivered to entire at-risk populations through a strategy known as mass drug 
administration (MDA). Ivermectin and albendazole are administered in areas where 
onchocerciasis is co-endemic; diethylcarbamazine and albendazole are administered in areas 
where onchocerciasis is not co-endemic. 
Results of a pilot study in Papua New Guinea suggest that triple drug therapy (ivermectin, 
diethylcarbamazine and albendazole) [2] is superior to the currently recommended two-drug 
regimen) [3]. A single dose of the triple therapy rapidly achieved complete clearance of 
Wuchereria bancrofti microfilariae from the blood of 12 individuals for at least one year post-
treatment. All six individuals tested at 24 months were still amicrofilaremic, suggesting that the 
triple therapy might permanently sterilizes adult filarial worms. Many people treated in these 
studies experienced transient systemic adverse events commonly associated with 
diethylcarbamazine or ivermectin treatment of filariasis. Adverse events were more frequent 
after the triple therapy than after the usual combination of two drugs. However, no serious 
adverse events were observed. Preliminary results from two larger clinical trials in Papua New 
Guinea and in Cote d’Ivoire (West Africa) are consistent with results from the pilot study. The 
dramatic reduction and sustained clearance of microfilaremia along with the safety profiles seen 
in these studies suggest that the triple drug therapy may be a useful tool for achieving the goal 
of eliminating lymphatic filariasis as a public health problem by 2020.  
Although the studies mentioned above have clearly demonstrated the superiority of the triple 
drug therapy for clearing W. bancrofti microfilariae from the blood, more safety and efficacy data 
are needed before triple therapy can be rolled out on a large scale as a mass drug 
administration regimen in lymphatic filariasis endemic countries. WHO recommends a best 
practice called “cohort event monitoring” for demonstrating safety of new drug regimens for 
public health program use. Establishing safety through such methodology requires pre and post 
treatment assessments from at least 10,000 people treated with the triple therapy across 
multiple settings.  
2.2 Country Specific Background 
Haiti is one of only four countries in the Americas where transmission of LF still occurs [4]. In 
2001, a national survey undertaken by the Ministère de la Santé Publique et de la Population 
(MSPP) and partners was able to show that approximately 90% of the Haiti’s 140 communes 
(district level) needed mass drug administration (MDA), representing an at-risk population of 
nearly 8 million people. Figure 1 shows the results of the 2001 LF mapping by commune divided 
between colored zones. The red zone or zone rouge represents the areas with highest 

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transmission. Following the completion of mapping, the MSPP established three goals for the 
National Program to Eliminate LF: (1) to interrupt transmission, (2) to reduce the suffering of 
persons with clinical and chronic manifestations of LF, and (3) to encourage positive health 
behaviors [5]. The MSPP National Neglected Tropical Diseases (NTD) Strategic Plan specifies 
that the goal is to eliminate LF in Haiti by 2020.  Haiti follows the LF strategy for elimination 
through consecutive MDAs with diethylcarbamazine (DEC) and albendazole for at least five to 
six years [6]. Even though LF was not identified in every commune, all communes were targeted 
for MDA. In 2000, MDA first started in Léogâne under the umbrella of a CDC-funded 
demonstration project [7]. In 2012, MSPP achieved 100% geographic coverage. Because of a 
gap in funding, national coverage did not continue in 2013, when 13 communes were untreated. 
In 2014 and 2015, MSPP was once again able to reach 100% geographic coverage with funding 
and technical support from its partners USAID (through the ENVISION project), the University of 
Notre Dame, and the Centers for Disease and Control and Prevention (CDC).  
Figure 1: Lymphatic Filariasis Baseline Mapping by Commune in Haiti, 2001 
 
Haiti has made significant progress in reaching its program goals. In 2015, MSPP carried out LF 
transmission assessment surveys (TAS) in 48 of Haiti’s 140 communes, with 46 of them 
passing the TAS successfully. Only four communes did not pass the pre-TAS, which aimed at 
demonstrating that the ICT prevalence in a commune is <2% and that the commune is eligible 
to conduct the TAS. Five high-prevalence communes (zones rouges, Figure 1) have passed the 
TAS, which is remarkable given their high starting prevalence (14%–45%). Only two communes 
in the North Department (Limonade and Plaine-du-Nord) being part of the zone rouge failed the 
TAS in 2015, while another (Cap-Haïtien) passed marginally [8]. MDA will continue in these 

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communes and in the communes that did not pass the pre-TAS for a minimum of two years. 
Figure 2 represents the LF status by commune in 2016.  
Figure 2: Lymphatic Filariasis Program Status by Commune in Haiti, 2016 
 
Establishing safety for MDA through WHO defined “cohort event monitoring” requires pre- and 
post-treatment assessment from at least 10,000 people treated with IDA across multiple settings 
(3,000 from Haiti). The current two-drug MDA regimens were studied in closely monitored 
community trials in a similar manner before they were endorsed for widespread use in the 
GPELF. It is therefore proposed to conduct a cohort event monitoring study to acquire similar 
safety data in Haiti (Quartier Morin Commune) before the new IDA regimen can be used to 
accelerate LF elimination particularly in those communes where LF antigenemia remains ≥1%.  
 
 

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3 POTENTIAL RISKS AND BENEFITS 
3.1 Risks of Blood Draw 
Blood collection via finger prick is considered to be minimal risk and little or no discomfort is 
anticipated.  The risk of infection is minimized by the use of standard sterile techniques.  On 
occasion a participant may faint during or after the finger prick.  Study personnel will be alert to 
participant reactions after the blood collection and will provide aid as needed 
3.2 Risks of Study Drugs 
The combinations of ivermectin plus albendazole or DEC plus albendazole are widely used for 
MDA. There have also been clinical trials of DEC plus Ivermectin and for triple drug therapy that 
show no significant drug interactions. Risks of each study drug is summarized below:  
Diethylcarbamazine (DEC): The most common side effects reported are itching and swelling of 
face, headache, joint pain, unusual tiredness or weakness. These are transient. Less common 
are dizziness, nausea or vomiting. Fever, painful and tender glands in groin, neck and armpits 
or skin rash can occur, and are usually associated with high burdens of infection as judged by 
the level of blood microfilaremia.  
Albendazole (ALB): The most common side effects reported are headache, nausea, stomach 
pain and vomiting and are usually associated with heavy soil-transmitted helminths infections. 
Severe allergic reactions occur rarely, and include rash, hives, itching, difficulty breathing, 
tightness in the chest, swelling of the mouth, face, lips, or tongue, and dark urine. Mild elevation 
in liver transaminases can occur, but normalize with cessation of treatment. These AEs are 
usually associated with prolonged ALB therapy.  
Ivermectin (IVM):  The most common side effects reported are diarrhea, dizziness and nausea. 
Rare side effects include rash, hives, itching, difficulty breathing, chest tightness, swelling of the 
mouth, face, lips, or tongue, eye pain, fainting, and fast heartbeat. Mild decrease in leukocyte 
counts, elevated liver function tests, and cardiovascular effects that included tachycardia and 
orthostatic hypotension have been described. Infrequently, treatment can exacerbate bronchial 
asthma. These AEs are usually associated with prolonged therapy. 
3.3 Potential Participant and Community Benefit 
Infected individuals, who sign an informed consent, will be treated for the LF infection. LF 
transmission to the community will be reduced by participation in either treatment arm.  A 
broader community benefit may be facilitated by the triple drug regimen as it is believed the 
triple drug regimen has the potential to markedly reduce the number of MDA treatments needed 
to achieve transmission interruption and elimination of LF.  

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Both regimens provide treatment for intestinal worms, and the triple drug treatment has the 
added benefit of providing an effective treatment for scabies.  
If the triple drug intervention proves successful, the triple therapy is likely to be adopted in many 
LF endemic areas globally. In order to facilitate such an uptake of triple therapy into national 
treatment policies, the study will be performed by the Coordinator of the LF and Malaria National 
Programs (MSPP), Dr. Jean Frantz Lemoine and results from this study will be combined and 
shared with the World Health Organization. 
3.4 Participant Participation and Cost  
Participation is voluntary and participants may decline participation without consequences.  
There will be no cost to the participant to participate in the study and they will not be paid for 
their participation.  The study will cover cost associated with laboratory test, study drugs, and 
clinical monitoring. 
3.5 Compensation for Injury 
The study drugs have been widely used for treatment of LF and it is anticipated that injury 
resulting from treatment will be rare.  In the event that a participant experiences a serious 
adverse event (SAE) attributable to study treatment, the project will help in supporting the 
medical treatment and/or hospitalization required.  
4 STUDY DESIGN AND OBJECTIVES 
4.1 Study Objectives 
4.1.1 Primary objective 
To determine the frequency, type and severity of adverse events following triple-drug therapy 
(IVM+DEC+ALB, IDA) compared to the standard two-drug treatment (DEC+ALB, DA) in infected 
and uninfected individuals in a community. 
4.1.2 Secondary Objectives 
1. 
To compare the efficacy of IDA vs. DA administered in communities for clearance of MF 
and filarial antigenemia. 
2. 
To assess the effect of intensity of filarial infection on the frequency and severity of 
adverse events. 
3. 
To compare community acceptance of MDA with IDA vs. DA. 

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4.2 Study Design 
The trial will be an open labelled two-armed study. The two arms are (1) MDA with IDA (triple 
drug therapy) and (2) MDA with the currently used combination of DA (two-drug regimen). An 
overview of the study flow is provided in Appendix 1. 
The primary endpoint will be the rate of AE and SAE among participants. The definitions of mild, 
moderate, severe and serious AE are provided in Appendix 4.  
4.3 Study Screening and Enrollment 
4.4 Study Sites 
The study will be conducted in the commune of Quartier Morin in the Northern Department. The 
baseline ICT prevalence in the commune of Quartier Morin was 39% (2001). In 2014, seven 
rounds of consecutive MDA had been conducted. The same year, the commune failed the pre-
TAS. The pre-TAS consists of collecting data in a sentinel site and in a spot check site at least 
six months after the fifth round of MDA to assess whether the TAS should be implemented. 
Ideally, the sites should collect data from 300–500 individuals aged over 5 years chosen from 
an area of known high transmission or from an area where difficulty in achieving high drug 
coverage is anticipated. The results of the assessment should show the prevalence of 
microfilaraemia to be <1% or the prevalence of ICT to be <2% in all sites in order to be eligible 
for the TAS. In the commune of Quartier Morin, the ICT prevalence found during the pre-TAS 
was 4.2% (21/496) of which of which 38% were MF positive (8 positive, 1.6% of all tested). 
4.5 Preparatory Activities 
4.5.1 Social Mobilization 
Prior to the administration of the drugs, intense social mobilization activities will be conducted to 
ensure maximum community participation. This will include development and distribution of key 
messages that will emphasize the acceptance and swallowing of the drugs along with their 
benefits and safety.  
Print and electronic mass media, people-based and folk media (e.g. sound trucks) will be used 
in the social mobilization campaign. Interpersonal communication using tool kits will play an 
important role utilizing the opportunity provided during enumeration and other preparatory 
activities.  

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4.5.2 Household Enumeration, Census and Geo-Referencing 
Health workers with the research team and community drug distributors (CDD) will enumerate 
and record the GPS coordinates of each house and compound within the selected study areas  
(House Visit #1, Appendix 1). A census will be performed to collect name, age and sex of each 
household member. Basic information on house structure that might affect mosquito exposure 
to lymphatic filariasis infection, e.g. type of structure, whether screened windows present, 
existence of a toilet, running water, electricity and/or insecticide treated bed nets will also be 
collected.  
4.6 Pre-Treatment Assessment Team 
The pre-treatment assessment (House visit #2, Appendix 1) team will be composed of 
individuals with basic medical training able to perform a medical history and a basic physical 
examination (local health workers, physicians, and nursing or medical students), laboratory 
technicians, and community drug distributors involved in previous MDA for LF and known by the 
local community. 
4.6.1 Inclusion and Exclusion Criteria 
Inclusion Criteria 
1. Age ≥ 5 years, for IDA and DA arms (males and females).  
2. Able to provide informed consent or give parental consent for minors to participate in the 
trial  
3. No evidence of severe or systemic co-morbidities except for features of filarial disease  
Exclusion Criteria 
1. Age < 5 years (ivermectin is not approved for use in children less than 5 years of age) 
2. Unable to provide informed consent or give parental consent for minors to participate in 
the trial 
3. Pregnant women (DEC, ivermectin and albendazole are not known to be safe for use 
during pregnancy) 
4. Severe chronic illness (chronic renal insufficiency, severe chronic liver disease, or any 
illness that is severe enough to interfere with activities of daily living) 
5. History of previous allergy to MDA drugs 

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4.6.2 Pregnant Females 
Pregnant females will not be eligible to participate in this study because of the unknown effects 
of the drugs and drug combination used in this study.  Females will be asked about the timing of 
the first day of their last menstrual period. Females who report that their last menstrual period 
started 4 weeks or longer before the interview will be excluded from the study. Females who do 
not recall the timing of their last menstrual period will also be excluded. 
4.6.3 Informed Consent 
All participants will provide written informed consent before any study procedures are done. 
Participation of minors (7−17 years of age) will require their assent and the written consent of at 
least one parent. Participants will sign a written, informed consent before the inclusion process 
(Appendix 6).  In the event that a participant is unable to read or has insufficient level of 
knowledge to comprehend the consent form, another person (family member, neighbor or other 
community member) with sufficient reading and writing skills will act as a witness to the 
consenting process. The witness should not be involved in the implementation of the study. 
Before they give their consent, individuals will be evaluated to know if they meet the study 
inclusion/exclusion criteria. Copies of the information sheet and of the consent/assent form will 
be given to each participant. The phone number to call would an AE occurs will be at the bottom 
of the informed consent. 
A waiver of consent is being requested for the Census and Geo-referencing portion of the study 
prior to receiving formal consent.  The study team will be collecting information about the 
communities and residents.  This portion of the study is not greater than minimal risk and the 
members of the study team who are conducting the Census and Geo-referencing portion of the 
study will explain what they are collecting to village residents. 
4.6.4 Baseline Survey 
After consenting and prior to evaluation for LF infection and treatment, all individuals will be 
assigned a unique ID and be enrolled using a participant enrollment form (Appendix 2). 
Questions will be asked to each participant about their general health and last menstrual period 
(to establish pregnancy for women of childbearing age). Each individual will be asked if they 
have signs of LF complications (hydrocele, lymphedema, lymphangitis, and lymphadenitis), if 
they took treatment during the previous MDA for LF and if they recently took albendazole, 
diethylcarbamazine, or ivermectin for other conditions. Participants reporting lymphedema will 
be examined to identify the location of the lymphedema. Participants will also be examined for 
scabies. Finally, participants will also be evaluated for the same AE than those evaluated after 
the treatment (Appendix 2). 
 

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4.6.5 Screening for Filarial Antigenemia and Microfilaria 
Approximately 75µl of capillary blood from each eligible individual will be collected via finger 
prick to be deposited on the rapid diagnostic test Filariasis Test Strip (FTS, Alere™, WHO 
approved) for LF antigen detection in the field. Participants with positive FTS tests will be visited 
at night (10 - 12 am) for microfilaria testing (60 μl measured volume blood smear- 3 lines, 
prepared according to the project Standard Operating Procedure (SOP)) collected by the finger 
prick method. 
Additionally, 60µl of capillary blood will be applied to a filter paper. The dried filter disks will be 
stored in a cool, dry place until used for testing.  Study participants will be informed that their 
blood on filter paper will be tested for LF antibody and potentially for other diseases of public 
health importance and will be shipped to the United States and stored for a longer time after the 
intended testing. No HIV or genetic testing will be performed. 
Universal precautions for individuals collecting and working with blood samples to include 
proper disposal of contaminated materials (test strips, lancets, capillary tubes, blood film slides) 
will be in accordance with the guidelines prescribed by the local health authorities. 
4.6.6 Randomization 
Communities will be assigned treatment either by randomization or by purposively matching 
communities based on population and prevalence of LF. If the prevalence is homogenous 
across the communities, each site may be randomly assigned to one of the two treatment arms. 
If the prevalence is heterogeneous, communities will be selected into each arm so that the 
population and prevalence between the two treatment arms is similar. 
4.7 Withdrawal 
Participation in this study is completely voluntary, and participants may terminate participation at 
any time.  Also if the well-being of the participant is compromised in any way, based on the 
opinion of the investigator, the participant can also be withdrawn from the study.   Even if the 
participant leaves the project early, we will encourage them to contact us at any time within the 
month after treatment to report any possible study-related AEs. 
4.8 Efficacy and Effectiveness of IDA vs DA 
One year post MDA, all participants who were positive for either microfilaremia or filarial 
antigenemia (FTS) during the baseline visit will be tested for filarial antigen using the FTS to 
assess their response to treatment and to compare the efficacy of the two treatment regimens. 
Participants with positive FTS will also be tested for nocturnal microfilaremia by blood smear 
(finger prick).  

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Additionally, for all participants who were positive for filarial antigenemia, 60µl of capillary blood 
will be applied to a filter paper. The dried filter disks will be stored in a cool, dry place until used 
for testing.  Consenting participants will be informed that their blood on filter paper will be tested 
for LF antibody and potentially for other diseases of public health importance and will be 
shipped to the United States and stored for a longer time after the intended testing. No HIV or 
genetic testing will be performed. 
4.9 Retreatment 
Any individual who tests positive for lymphatic filariasis at 12 months (by microscopy or antigen 
test) will be re-treated with the standard MDA regimen (single dose of DEC with Albendazole). If 
triple drug therapy (IDA) is recommended by the WHO or by national regulatory agencies for 
lymphatic filariasis and if investigators have adequate supply of ivermectin, infected individuals 
may be offered IDA. This practice is meant to ensure that all participants who participated in the 
study may get the most beneficial treatment. Pregnant women will not be eligible for re-
treatment because of the unknown effects of drug combination used to treat LF. They will be 
advised to participate to the MDA organized by the MSSP after their delivery. 
4.10 Guidelines for Stopping the Trial 
There are no pre-specified criteria for terminating the study early. 
Upon review of the data for the trial, the data and safety monitoring board (DSMB) will make 
decisions regarding the continuation of the trial.  The final decision to stop the trial is left to the 
recommendation of the DSMB.  If the DSMB recommends discontinuation or modification of the 
study, the Chair of the DSMB will meet or talk with the DOLF Project Team at the earliest 
opportunity to review the basis for the recommendation. The study should be stopped if a 
treatment arm shows a significant increase in unacceptable side effects that would include, 
death, fever, and nausea that persist more than a day and would require hospitalization.   
4.11 Triple Drug Regimen Acceptability 
A survey to assess the treatment acceptability in the community is planned to follow the safety 
trial. The overall aim is to understand the community’s acceptance of the 3-drug regimen as well 
as gain insight into the feasibility of administering this new therapy in the future. Part of the 
investigation will include assessing community member’s perception of the possible side effects 
experienced as a result of the 3-drug therapy compared to the 2-drug therapy, and how that 
might affect future rounds of mass drug administration (MDA) at the community level. 
Community acceptance will be measured using a survey to community members receiving both 
the 2-drug and 3-drug treatments during the safety trial. The survey participants will be identified 
from the roster of individuals enrolled in the safety trial. To complement this survey, a series of 
focus group discussions in the community as well as key informant interviews are proposed with 

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community leaders, health personnel and drug distributors in the same communities to assess 
perceptions about the 3-drug versus the 2-drug regimen. The community acceptability study will 
be carried out within one month of the completion of the safety trial. The protocol for the 
acceptability survey is included in of this protocol. The community questionnaire and topic 
guides will be submitted to the ethical committee for approval as an amendment prior to 
implementation of the survey. 
 
 

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5 INVESTIGATIONAL PRODUCT 
Each of the drugs used in this study is approved for human use and has a prior history of use in 
the treatment of LF.   
5.1 Study Drug Background 
Albendazole (ALB) has been known to cause degenerative alterations in the tegument and 
intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its 
polymerization or assembly into microtubules [9]. The loss of cytoplasmic microtubules leads to 
impaired uptake of glucose by larval and adult stages of the parasite, and depletes glycogen 
stores. Degenerative changes in endoplasmic reticulum and mitochondria of the germinal layer, 
and the subsequent release of lysosomal enzymes result in decreased production of adenosine 
triphosphate, which is the source of energy required for survival of the helminth. Due to 
diminished energy production, the parasite is immobilized and eventually dies. Adverse events 
are uncommon in persons who are treated with a single dose of albendazole (apart from AEs 
that result from parasite death). Some patients report mild gastrointestinal AEs such as nausea 
after ingesting the tablet. 
Ivermectin (IVM) is an avermectin compound of macrocyclic lactones derived from the 
bacterium Streptomyces avermitilis [10]. The mechanism by which IVM kills LF microfilariae is 
not known with certainty, but the drug interferes with glutamate gated ion channels that can 
affect parasite contractility and release of immunomodulatory molecules by the parasite [11]. 
IVM also has a direct effect on the central nervous system and muscle function of worms as it 
enhances strength of inhibitory neurotransmission pathways.  The main concern with the use of 
IVM in animals and humans is neurotoxicity, which can be manifest as ataxia. Neurotoxicity has 
not been observed in humans given single dose IVM for LF or other parasitic infections. IVM 
has been used to treat millions of people with LF and onchocerciasis. Peak IVM serum 
concentrations are reached approximately 4-5 hours after administration. The half-life of IVM in 
various populations ranges from 12 to 56 hours [12]. There is no evidence of drug: drug 
interaction between ALB and IVM [13]. IVM can cause nausea, dizziness and occasionally 
pruritus, but these are infrequent, transient and usually mild. Serious adverse events have 
occurred in patients with heavy Loa loa infections. 
DEC (diethylcarbamazine citrate) is an anthelminthic drug that is structurally distinct from ALB 
and IVM [14]. DEC inhibits arachidonic acid metabolism by LF, and inducible nitric oxide 
synthase and the cyclooxygenase pathway may be essential for activity in vivo [14]. DEC also 
has anti-inflammatory properties. The mechanisms of action of DEC remain poorly understood. 
Its ability to kill MF and adult worm depends on the host immune responses since the drug has 
little direct activity on parasites in vitro. The drug has potent activity against LF microfilaria. DEC 
has about 50-70% [15] efficacy in killing or sterilization of adult worms. The drug is rapidly 
absorbed from the gastrointestinal tract, has a serum half-life of 12 to 14 hours, and is excreted 

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in the urine with little modification by liver metabolism. Adverse events from DEC are unusual 
apart from those that result from killing filarial worms.  
5.2 Product Supply and Storage 
Only WHO approved drugs will be used in this study. DEC and albendazole will be provided by 
the Haiti Lymphatic Filariasis Elimination Program through the WHO. A request will be 
submitted to the manufacturer Merck to provide ivermectin for the present study. Alternatively 
WHO approved generic ivermectin may be purchased. 
All three study drugs are approved and distributed globally by WHO as part of GPELF. Detailed 
information for each drug is available from the pharmaceutical manufacturer. All products should 
be maintained at ambient temperature, if possible <30 °C.  
5.3 Triple Drug Therapy (IDA) and Two-Drug Therapy (DA)  
The triple-drug combination will consist of a single dose of ivermectin (200 µg /kg), DEC 
(6mg/kg) and albendazole (flat dose of 400 mg). The two-drug combination will consist of a 
single dose of DEC (6mg/kg) and albendazole (flat dose of 400 mg). Study personnel will 
directly observe oral administration of drugs. Drugs will be given after the informed consent has 
been obtained. The study population will be encouraged to eat before swallowing the medicine 
(without chewing the tablets) with a glass of water. Vomited doses will be replaced. Drug 
administration will be supervised (directly observed treatment or DOT) to ensure that all enrolled 
individuals swallow the drugs.  
6 SAFETY REPORTING AND SAFETY MONITORING 
The post-treatment assessment team will be composed of individuals with basic medical training 
who are able to perform a medical history and a basic physical examination (physicians, local 
health workers, nursing and/or medical students). Physicians from the area will be available to 
assist in the evaluation and management of adverse events. 
6.1 Definitions 
Adverse Event (AE)  
Any untoward medical occurrence in a clinical investigation participant who has received a study 
product intervention and that does not necessarily have to have a causal relationship with the 
study product. An AE can, therefore, be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom, or disease temporally associated with the 
use of a study medicinal product, whether or not considered related to the study medicinal 
product. 

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An AE does not include: 
 
Medical or surgical procedures (e.g. surgery, tooth extraction, transfusion). The condition 
that leads to the procedure is an adverse event 
 
Pre-existing diseases or conditions or laboratory abnormalities present or detected prior 
to the screening visit that do not worsen 
 Serious Adverse Event (SAE)  
A SAE is any adverse event that results in any of the following outcomes: 
 
Death; 
 
Life-threatening (immediate risk of death); 
 
Inpatient hospitalization or prolongation of existing hospitalization; 
 
Persistent or significant disability or incapacity; 
 
Congenital anomaly/birth defect; 
 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered a serious adverse event when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasia or 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Unexpected 
An adverse reaction, the nature or severity of which is not consistent with the applicable product 
information (e.g., Package Insert). 
Expedited Safety Report  
Documentation in appropriate form and format summarizing an SAE that meets expedited 
safety reporting criteria, submitted within the required reporting time frame of applicable 
regulatory authorities and/or IRBs/IECs of participating countries. 
6.2 Assessment of Adverse Events 
Adverse event monitoring will be performed approximately 24 and 48 hours following drug 
administration (late afternoon and evenings following treatment, house visit #3 and 4, Appendix 
1). All dosed participants will be followed for adverse events through Day 7. 

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Evaluations will be documented on pre-printed Patient Monitoring forms (Appendix 3) using the 
scoring instructions for AEs (Appendix 4) or entered directly into an electronic form using tablet 
computers.  
Most adverse events after MDA are associated with killing of MF and are seen in the first 12-
24h following treatment. However, occasional adverse events related to adult worm death may 
be delayed by several days.  
To capture these adverse events and to assure that any systemic adverse events that occurred 
earlier have resolved, study personnel will also visit study villages daily on days 3 through 7 
after treatment (passive AE monitoring). Individuals with AEs that interfere with activities of daily 
living (grade 2 or higher) will have more detailed assessments that will include a brief physical 
examination (including measurement of temperature, blood pressure and pulse).  
6.3 Serious Adverse Event (SAE) Assessment and Management 
Study participants with definite or suspected serious AEs (any event ≥ grade 3) will be referred 
to a physician or appropriate health care professional for evaluation. These evaluations will be 
documented with special adverse event evaluation forms (Appendix 5), following the instructions 
(Appendix 5a).  
An SAE may qualify for reporting to regulatory authorities if the SAE is possibly attributable to 
one or more of the study drugs, and is unexpected based on the Company Core Safety 
Information.   
The investigator should notify the Institutional Review Board (IRB) or Ethics Committee (EC) as 
soon as is practical, of serious events in writing where this is required by local regulatory 
authorities, and in accordance with the local institutional policy. 
6.4 Reporting of Pregnancy  
Pregnancy is an exclusion criteria for this study. Although not AEs, pregnancies are reportable 
events. In the event that a pregnant woman is inadvertently dosed efforts will be made to follow-
up and ascertain and report the pregnancy outcome (e.g., any premature terminations, elective 
or therapeutic, and any spontaneous abortions or stillbirths, as well as the health status of the 
mother and child including date of delivery and infant’s gender and weight). Any pregnant 
woman inadvertently dosed who has a miscarriage or spontaneous abortion within the week of 
follow-up will be reported as an SAE.   
6.5 Safety Monitoring by the Oversight Committee 
A DSMB consisting of 4 experts (including 3 physicians) knowledgeable in neglected tropical 
diseases will be in place to monitor the safety data per country and across countries 
participating in the DOLF project. 

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6.6 Country Specific Safety Reporting  
The medical monitor will forward SAE reports to the PI in Haiti within 48 hours, and to the data 
safety review board (DSRB). All SAEs will be reported to the Haitian Bioethical Committee 
within 7 days. 
7 CLINICAL MANAGEMENT OF EVENTS 
Individuals who have basic medical training (physicians and/or nursing or medical students) and 
who are able to complete and pass a training course will be responsible for the initial adverse 
event evaluations.  
In the case of mild symptomatic reactions local health workers/study personnel will provide 
antipyretics/analgesics and anti-allergic agents at the time of follow-up. It is anticipated that the 
majority of adverse events will resolve within a day or two and will not require treatment.  In the 
initial adverse event monitoring if any of the following are noted a physician will be notified to 
evaluate the participant for a potential serious adverse event: 
 
Participant reports they are unable to participate in their normal daily activities 
 
Participant has or reports a temperature >39ºC 
 
Participant has or reports a significant drop in blood pressure 
 
Participant has other significant objective findings that should be referred to a physician 
All grade 3, 4 and 5 events or overnight hospitalization will require completion of the Adverse 
Event Evaluation and Report Form (Appendix 5). The physician will provide any required 
immediate treatment and facilitate admission into the hospital or health center as deemed 
appropriate. 
7.1 Adverse Event Monitoring and Management 
Adverse Event monitoring and management will follow or exceed WHO guidelines.  Participants 
will be visited on the two days following treatment by study personnel with medical training.  
Formal assessment of adverse events (with a standard form) will take place on days 1 and 2 
and later if symptoms persist or start late.   
Study personnel will use the toxicity table (Appendix 4) to score adverse events for severity.  
Study personnel will visit each study area daily for 7 days following MDA treatment to manage 
any adverse events as follows:   
7.1.1 Mild Localized Symptoms 
Participants who develop painful lymphadenopathy, scrotal pain or painful swelling or nodules 
along lymphatic vessels will be treated with acetaminophen or ibuprofen. 

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7.1.2 Moderate to Severe Localized Adverse Events 
Participants with more severe local adverse effects (≥ Grade 3, Appendix 4) like acute swelling 
or severe scrotal pain that is not relieved by acetaminophen will be transported by study 
personnel to the medical facility identified for the study for evaluation by one of the physicians or 
other qualified medical personnel involved in the study. If necessary, participants will be 
transferred (after stabilization) to the Departmental Hospital. 
7.1.3 Moderate Systematic Adverse Events 
Subjects who develop commonly observed symptoms of fever, myalgia, or headache will be 
advised to rest and will be treated with acetaminophen. Subjects who develop lightheadedness 
or dizziness will be advised to remain at bed rest until the symptoms have resolved. Subjects 
who develop nausea or vomiting will be advised to take a clear liquid diet. Antihistamine will also 
be available for persistent cases. 
7.1.4 Moderate to Severe Systemic Adverse Events 
Participants with more severe systemic adverse effects (fever over 39 C > 72 hours, other 
adverse events ≥ Grade 3, syncope, jaundice, or any condition that might require 
hospitalization) will be transported by study personnel for physician or other qualified medical 
personnel evaluation at the medical facility identified for the study. If necessary, participants will 
be transferred (after stabilization) to a local hospital. Serious adverse events will be followed 
until resolution. 
7.2 Rapid Response Teams for Management of Adverse Events 
Medical teams will be located at strategic places close to the study sites. Participants, and 
persons involved in the study (inclusion process and AE monitoring) will be informed about the 
location and phone numbers of these teams so that they can report directly to these teams if 
necessary. These teams will be in position from the day of drug administration until the 
completion of operations. 
8 STATISTICAL CONSIDERATIONS 
All participants receiving study drug will be included in both the safety and efficacy analysis 
8.1 Safety  
The sample size of 3000 participants in each arm in Haiti will contribute to the total sample size 
for the project. The WHO requires a total of 10,000 participants to detect a SAE rate of 0.1% for 
each of the treatment regimens and recruitment in other countries (e.g., India, Fiji, Indonesia, 
Papua New Guinea, and Sri Lanka) is planned to contribute to the overall sample size required. 

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It is well known that systemic AEs are related to killing of MF and that the severity of AEs is 
related to MF counts. Since MF rates in the study area are relatively low, the Haiti study alone 
will not be powered to compare rates of SAEs between MDA regimens.  
The primary endpoint for safety studies will be the rates of SAEs that occur in infected and in 
uninfected participants within the first 7 days post MDA. Total AEs will be a secondary endpoint 
for the study.  
8.2 Efficacy 
Assuming an MF-prevalence of 1% in the study population at baseline, the survey is expected 
to detect at least 30 MF positive participants in each arm. A minimum of 21 (70%) of these MF-
positive participants in each arm will be retested at 12 months post-treatment for antigenemia 
and microfilaremia. This sample size is adequate to demonstrate superiority of the IDA regimen 
(assumptions: 90% reduction in MF prevalence after IDA and 60% reduction after DA, 80% 
power for detecting an effect size of 30%). The primary endpoint for efficacy will be complete 
clearance of MF 12 months post MDA. Clearance of filarial antigenemia at 12 months will be a 
secondary endpoint for the efficacy analysis. 
8.3 Enrolling Additional Participants 
It is possible that recruitment in other countries may be less than anticipated. In this case the 
number of participants enrolled in this study may need to be increased to make up for the loss in 
another country. The number of additional people enrolled will be no more than is necessary to 
reach the total of 10,000 participants treated with IDA. In this situation the principal investigators 
will inform the ethics review committees of the expanded enrollment. 
 

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9 DATA HANDLING/RECORD KEEPING/SOURCE DOCUMENTS 
Data will be collected using a tablet based system, pre-loaded with study templates.  Field 
teams will be trained in the use of the instruments and data will be uploaded as entries are 
completed. 
9.1 Types of Data Collected 
Enrollment Data will include (Appendix 2): 
 
Site Identification 
 
Participant Identifier 
 
Informed Consent Date 
 
Demographic Information 
 
Pregnancy/last menstrual period 
 
Medical History 
 
Presence of hydrocele and lymphedema 
 
Bed net and window screen use 
 
History of prior MDA treatment 
 
Pre-treatment adverse event assessment 
 
Limited Physical Exam 
Laboratory Results   
 
FTS (filarial antigen test)  
 
FTS score 
 
MF slide (including MF count) 
Participant Monitoring Forms (24 & 48 hour post treatment): 
 
Adverse Event Assessment 
 
Physical Examination, as appropriate 
Adverse Event Evaluation and Report (Appendix 5) 
 
Participant Identification 
 
MDA Treatment 
 
Concomitant medication taken at the time of the MDA 
 
AE Description,  
 
Start and Stop Date 
 
Outcome 
 
SAE Evaluation and causality to MDA (definite, probable, possible, or unrelated) 

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9.2 Study Records Retention  
Study documents will be retained for a minimum of three (3) years after the last participant has 
completed the study.  These documents will be retained for a longer period, however, if required 
by local regulations. No record will be destroyed without the written consent of DOLF. 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with ICH E6, Section 4.9, regulatory and institutional requirements for the protection 
of confidentiality of participants. Each site participating in this study will permit authorized 
representatives of the sponsor and regulatory agencies to examine (and when required by 
applicable law, copy) clinical records for the purposes of clinical site monitoring, quality 
assurance reviews, audits, and evaluation of the study safety and progress.  
9.3 Source Documents 
This study will use both paper and electronic source and this may vary by location due to local 
availability.  All sites will be provided with hard copy data collection forms derived from the 
electronic case report form (CRF).  If data is first entered on paper, the study staff will enter the 
data into the electronic capture system. 
10 RESPONSIBILITIES 
10.1 Investigator Responsibilities 
10.2 Good Clinical Practice 
The investigator will ensure that the basic principles of Good Clinical Practice are followed along 
with the appropriate laws and regulations of the country in which the research is conducted.  
10.3 Institutional Review Board (IRB)/Ethics Committee (EC) 
The protocol and any accompanying material to be provided to the participants, such as the 
informed consent, will be submitted to the EC for review and approval.  Approval from the ethics 
committee must be obtained before starting the study and should be documented in 
correspondence to the investigator. 
Any modifications to the protocol after receipt of the IRB or EC approval must be submitted to 
the committee for approval prior to implementation. 

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10.4 Informed Consent 
It is the responsibility of the investigator to obtain written informed consent from each individual 
participating in the study after adequate explanation of the aims, methods, objectives and 
potential risk of any study related procedures.  The investigator must use an IRB/EC approved 
informed consent form (Appendix 6).  The investigators will accept either signed (cursive) or 
printed signatures or a witnessed mark in the case of illiterate study participants on the consent 
form. 
Only the principal investigators or study staff authorized and certified to obtain consent will 
consent participants for this study.  Only individuals who have signed the consent form and 
meet eligibility criteria will be enrolled in the study.  
Entry into the study and participation will be strictly voluntary.  It will be made clear that refusal 
to participate or a decision to withdraw can occur at any time throughout the course of the study 
and will not influence their rights or the care they receive at local health facilities. Potential 
participants will be told that all of their health information will be confidential and that records will 
be coded without personal identifiers before they are shared with statisticians or project 
scientists outside of the village/region/country. They will also be told that no monetary or other 
gains are offered in exchange for participation apart from compensation for time and 
reimbursement of travel expenses as described above.  
10.4.1  Informed Consent Training 
The PI, co-PIs and the site project coordinator will conduct on-site training sessions for Haitian 
study personnel who will be collecting study information, specimens, and obtaining consent from 
participants in the study. Each step of the study will be explained in detail to the local study 
personnel. The basic principles of informed consent process, documentation of informed 
consent, protection of participants’ rights, confidentiality, and handling of data will be covered in 
these training sessions. Study personnel will be monitored by the on-site project coordinator on 
a regular basis to ensure compliance with the principles of informed consent. The investigators 
and study personnel who will obtain consent from study participants will also receive training in 
the informed consent process and good clinical practices (GCP). 
10.4.2 Country Specific ICF Information  
The study will be discussed with Ministry of Public Health representatives and senior community 
members to assess both feasibility and community acceptability of the study design and field 
procedures. Community leaders will first give their authorization to include their community in 
the study.  

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All consent forms and study information material will be translated in Creole. All study personnel 
involved in the inclusion process of participants and in AE monitoring will be fluent in Creole and 
French. The informed consent process recognizes the community and cultural values of Haiti 
and the commune of Quartier Morin where the study participants reside. Extensive discussion of 
risks and possible benefits of participation in this study will be provided to the study participants.  
Formal, written informed consent will be obtained for individuals willing to participate in the 
study.  The Haitian Ethical Committee (Comite National de Bioéthique) will approve the 
informed consent form.  The participant will be asked to read, or have read to them, and review 
the informed consent documents. Upon reviewing the document, the investigator and/or study 
staff will explain the research study to the participant and answer any questions that may arise. 
The investigators will accept either a participant signed (cursive) or printed signatures or a 
witnessed signed (cursive) or printed signatures if the study participant is illiterate.  
Only the principal investigators or study staff authorized to obtain consent will consent 
participants for this study.  Only individuals who have signed the consent form and meet 
eligibility criteria will be enrolled in the study.  
10.5 Participant Privacy  
Privacy of the study participants will be maintained by assigning study participants a unique 
study identification number (UNID). All data, blood samples and laboratory results will be 
recorded and analyzed by UNID with no personal identifiers.  All information collected, including 
demographic information about enrolled participants will be kept confidential and available only 
to the investigators and authorized study personnel such as the data manager. 
Though most data will be collected on tablets, all written forms (i.e., consent and any paper data 
collection forms) will be stored in a designated locked area with limited control. All forms will be 
labelled and filed in cabinets with the study protocol number, PI’s names and collection dates. 
These cabinets will be metal and have functioning locks. Keys will be kept with the Project 
Coordinator.  All electronic devices on which data are entered will be password protected. PIs 
and/or the Project Coordinator will authorize access. The paper forms will be stored for the 
duration of the study plus three years per IRB protocol for primary data storage. 
10.6 Data Ownership 
The data are the property of MSPP. The Principal Investigators, Co-investigators and key 
personnel may use the results of this study for publications, presentations at scientific meetings 
or as preliminary data for subsequent grant applications. Confidentiality of study participants will 
be maintained by not using names or personal identifiers. MSPP will provide de-identified data 
from the study to DOLF for use in publications and presentations that present results across 
different study sites. At least one Haitian researcher will be included as an author for any 
publications with data from Haiti. 

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Protocol version date: 05 July 2017 
 
The study site Project Coordinator will permit access to all documents and records that may 
require inspection by the funding agencies, governmental regulatory agencies, institutional 
review boards or its authorized representatives.  
11 PUBLICATION POLICY  
Manuscripts should be submitted for publication no later than one year following the date of the 
“last patient/last visit”. This study includes follow-up data collection past the primary end point, 
including acceptability and efficacy results. It is not necessary to wait for the follow-up studies to 
be completed in order to publish the primary safety data. 
Endemic country investigators have an obligation to publish the results of DOLF studies 
conducted in their country. These results benefit the national NTD programs and the citizens of 
the country where the study was completed. DOLF collaborating institutions are willing to help 
their endemic country partners with the data analysis, manuscript preparation, publication fees, 
etc. However, the lead author should be an investigator from the country where the study was 
performed. 
DOLF scientists will be responsible for publishing the results from the aggregated data that 
combines the results from multiple study sites. The purpose of these manuscripts is to consider 
the similarities and differences in results obtained in different countries. These publications will 
not include as much detailed data or analyses as the country specific publications. Publications 
that report multi-country results will have at least one co-author from each country included in 
the manuscript. 
 
 

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Protocol version date: 05 July 2017 
 
12 LITERATURE  REFERENCES 
 
1. 
World Health Organization (1997). Elimination of lymphatic filariasis as a public health 
problem - resolution of the executive board of the WHO. 
2. 
Thomsen, E.K., et al., Efficacy, Safety, and Pharmacokinetics of Coadministered 
Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis. 
Clin Infect Dis, 2015. 
3. 
Gyapong, J.O., et al., Treatment strategies underpinning the global programme to 
eliminate lymphatic filariasis. Expert Opin Pharmacother, 2005. 6(2): p. 179-200. 
4. 
Global programme to eliminate lymphatic filariasis: progress report, 2014. Wkly 
Epidemiol Rec, 2015. 90(38): p. 489-504. 
5. 
Oscar, R., et al., Haiti National Program for the elimination of lymphatic filariasis--a 
model of success in the face of adversity. PLoS Negl Trop Dis, 2014. 8(7): p. e2915. 
6. 
World Health Organization (2002). Global Programme to Eliminate Lymphatic Filariasis. 
Annual 
Report 
on 
Lymphatic 
Filariasis. 
Geneva: 
WHO. 
Available 
from: 
http://www.filariasis.org/pdfs/Press%20Centre/Reports/LF_Annual_Report_2002.pdf. 
7. 
de Rochars, M.B., et al., The Leogane, Haiti demonstration project: decreased 
microfilaremia and program costs after three years of mass drug administration. Am J 
Trop Med Hyg, 2005. 73(5): p. 888-94. 
8. 
Envision (2015). Haiti Work Plan, FY 2016, Project Year 5, October 2015-September 
2016. 
Available 
from: 
http://ntdenvision.org/resource/envision_reports_to_usaid/haiti_fy16_workplan.  
9. 
Horton, J., Albendazole: a review of anthelmintic efficacy and safety in humans. 
Parasitology, 2000. 121 Suppl: p. S113-32. 
10. 
Goa, K.L., D. McTavish, and S.P. Clissold, Ivermectin. A review of its antifilarial activity, 
pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs, 1991. 42(4): p. 
640-58. 
11. 
Edwards, G., Ivermectin: does P-glycoprotein play a role in neurotoxicity? Filaria J, 
2003. 2 Suppl 1: p. S8. 
12. 
Ottesen, E.A. and W.C. Campbell, Ivermectin in human medicine. J Antimicrob 
Chemother, 1994. 34(2): p. 195-203. 
13. 
Awadzi, K., et al., The co-administration of ivermectin and albendazole--safety, 
pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol, 
2003. 97(2): p. 165-78. 
14. 
Ottesen, E.A., Efficacy of diethylcarbamazine in eradicating infection with lymphatic-
dwelling filariae in humans. Rev Infect Dis, 1985. 7(3): p. 341-56. 
15. 
Noroes, J., et al., Assessment of the efficacy of diethylcarbamazine on adult Wuchereria 
bancrofti in vivo. Trans R Soc Trop Med Hyg, 1997. 91(1): p. 78-81. 
 
 

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13 LIST OF APPENDICES 
Appendix 1:  Study Flow Diagram (Country Specific) 
Appendix 2:  Participant Enrollment Form [Example] 
Appendix 3:  Participant Monitoring Form [Example] 
Appendix 4:  Guide to Assigning Adverse Event Severity 
Appendix 5:  Adverse Event Evaluation and Report Form (AEERF) [Example] 
Appendix 5a: Required Reporting & Guidelines for SAE(s) 
Appendix 6:  Information Sheet and Informed Consent Form [Example] 
 
 

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APPENDIX 1: 
STUDY FLOW DIAGRAM (COUNTRY SPECIFIC) 
 
 
 
 
 

 
 
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APPENDIX 2: 
PARTICIPANT ENROLLMENT FORM [EXAMPLE]  
Participant ID (Barcode): 
 
1. SITE INFORMATION 
Team (required): 
 
Data Entry Clerk ID (required): 
Enrollment Date (required) (DD-MM-YYYY): 
Consent Method (required) 
☐Self 
☐Parent 
☐Other guardian (specify): 
☐Teacher 
☐No consent (STOP) 
Enrollment Location 
☐Home 
☐School 
☐Village meeting point 
 
Enrollment Village:  
2. PARTICIPANT INFORMATION AND MEDICAL HISTORY 
Gender:   ☐M    ☐F 
Note: if exact date is not known, birth year is sufficient 
Age (Years): 
Birth Day (DD): 
Birth Month 
(MM): 
Birth Year 
(YYYY): 
Village of Residence: 
House Number: 
Participant ID (Barcode): 
(affix barcode at the top of each form AND write in ID number at top of each page) 
Females only:  When was the date of your last menstrual period? (read options) 
☐Definitely less than 4 weeks ago 
☐Post-menopause 
☐4 weeks of longer (STOP) 
☐Uncertain (STOP) 
Males only:  Do you have swelling or enlargement of your scrotum? 
☐Yes   ☐No 
Males only:  Do you feel pain in your testicles or scrotum?    
☐Yes   ☐No 
Do you have any of the following chronic medical conditions? (read options) 
☐Hypertension (high blood pressure) 
☐Asthma or chronic lung disease 
☐Chronic kidney disease (renal insufficiency) 
☐Diabetes 
☐Other (specify): 
Do you have swelling in your arms or legs (lymphedema)?    
☐Yes   ☐No 
If participant reports lymphedema exam them and confirm presence of edema.   
Left arm 
☐No edema ☐Yes edema  

APPENDIX 2: PARTICIPANT ENROLLMENT FORM [EXAMPLE] 
 
Participant ID (Barcode): 
 
 
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Left leg  
☐No edema ☐Yes edema 
Right arm  
☐No edema ☐Yes edema 
Right leg  
☐No edema ☐Yes edema 
Did you use a bed net last night?  
☐Yes   ☐No 
Does your house have screens on the windows? 
☐Yes   ☐No 
Do you spray indoors to prevent mosquitos? 
☐Yes   ☐No 
Did you swallow medicines during MDA treatment for filariasis in the last twelve months?  
(If YES enter the date) 
☐Yes 
Date of last MDA (MM-YYYY):___________    ☐Do not remember date 
☐No 
☐Uncertain 
☐N/A—no MDA distributed 
Have you ever taken the following medication called…? 
 
Albendazole? 
 
☐Yes  ☐No  ☐Don’t know 
 
Ivermectin?  
 
☐Yes  ☐No  ☐Don’t know 
 
DEC?  
 
☐Yes  ☐No  ☐Don’t know 
 
3. AE ASSESSMENT 
Today, were you too sick to work or go to school? 
☐Yes (exclude, but finish the pre-treatment assessment) 
☐No 
EXPLAIN: Now I will ask you some questions about your health during the past two days. 
In the past 2 days have you experienced…? 
..Fever 
☐Yes   ☐No 
..Dizziness, giddiness, or fainting 
☐Yes   ☐No 
..Confusion  
☐Yes   ☐No 
..Drowsiness 
☐Yes   ☐No 
..Headache 
☐Yes   ☐No 
..Cough 
☐Yes   ☐No 
..Difficulty breathing (wheezing or dyspnea)  
☐Yes   ☐No 
..Nausea 
☐Yes   ☐No 
..Vomiting 
☐Yes   ☐No 
..Diarrhea 
☐Yes   ☐No 

APPENDIX 2: PARTICIPANT ENROLLMENT FORM [EXAMPLE] 
 
Participant ID (Barcode): 
 
 
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..Stomach pain 
☐Yes   ☐No 
..Unusual swelling, beyond baseline lymphedema 
☐Yes   ☐No 
 
Specify Location:   ☐Arm   ☐Leg   ☐Breast   ☐Scrotum 
..Joint or muscle pain 
☐Yes   ☐No 
..Weakness 
☐Yes   ☐No 
..Swelling or pain in your armpit or groin  
☐Yes   ☐No 
..Men only:  pain in you testicles or scrotum 
☐Yes   ☐No 
..Itchy skin 
☐Yes   ☐No 
..Rash (specify location): 
☐Yes   ☐No 
Is the rash in the spaces between your fingers? 
☐Yes   ☐No 
..Other illness or symptoms (specify): 
☐Yes   ☐No 
Have you ever suffered from scabies? (note: use local name for scabies) 
☐Yes 
☐No 
☐Don’t know 
Additional notes or comments: 
4. EXAMINATION 
Team (required): 
Clinician (required): 
Data Entry Clerk ID (required): 
Measurements 
Values / status 
Height (cm) 
 
Weight (kg) 
 
BMI (calculated) 
 
Scabies 
☐Yes   ☐No 
 
If Yes, please take photograph 
 
 

 
 
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APPENDIX 3: 
PARTICIPANT MONITORING FORM [EXAMPLE] 
FOR: Day 1 & 2, if needed days 3-7 
 
Participant ID (Barcode): 
 
Use this form for active monitoring of adverse events on day 1 (24 hours) and 2 (48 hours) 
following therapy, as well as for recording symptoms reported by those presenting with 
complaints on days 3-7 post-treatment. 
Team (required): 
Clinician (required): 
Data Entry Clerk ID (required): 
1. PARTICIPANT INFORMATION 
Gender:   ☐M    ☐F 
Age (Years):  
Village of Residence: 
Treatment Village: 
Treatment Date (DD-MM-YYYY):                     
2. ASSESSMENT INFORMATION 
Day 1 and 2: All participants should be asked all the questions in Table 1. 
Days 3-7: Any participant who presents with a complaint should be asked all the questions in 
Table 1 
Table 1:  Reported Symptoms 
 
Record a symptom grade from 0-5 for each day on which the participant experienced 
symptoms.  
 
For participants reporting ANY symptom, complete every questions in Table 1.  
 
Refer to the Appendix 4 for symptom-specific scoring criteria. 
 
Anyone with a symptom typed in bold needs to have Table 2 completed. 
 
Symptom Grading 
0 = No adverse event or within normal limits 
1 = Mild adverse event, does not interfere with work or school 
2 = Moderate adverse event, interferes with work or school at least 1 day 
3 = Severe and undesirable adverse event; interferes with ADL, requires medical assessment 
4 = Potentially life-threatening or disabling adverse event; requires transfer to medical facility 
5 = Death  
 
Symptoms/Signs 
Since you took the tablets have you 
experienced…? 
Post-treatment day(s) on which symptoms 
or signs were present 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
..Fever 
 
 
 
 
 
 
 
..Dizziness, giddiness, or fainting 
 
 
 
 
 
 
 
..Confusion 
 
 
 
 
 
 
 
..Drowsiness 
 
 
 
 
 
 
 

APPENDIX 3: PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
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..Headache 
 
 
 
 
 
 
 
..Cough 
 
 
 
 
 
 
 
..Difficulty breathing (wheezing or dyspnea) 
 
 
 
 
 
 
 
..Nausea 
 
 
 
 
 
 
 
..Vomiting 
 
 
 
 
 
 
 
..Diarrhea 
 
 
 
 
 
 
 
..Stomach pain 
 
 
 
 
 
 
 
..Unusual swelling, beyond baseline lymphedema (specify location below)  
Arm 
 
 
 
 
 
 
 
Leg 
 
 
 
 
 
 
 
Breast 
 
 
 
 
 
 
 
Scrotum 
 
 
 
 
 
 
 
..Joint or muscle pain 
 
 
 
 
 
 
 
..Weakness 
 
 
 
 
 
 
 
..Swelling or pain in your armpit or groin 
 
 
 
 
 
 
 
..Men only: pain in your testicles or scrotum 
 
 
 
 
 
 
 
..Itching skin 
 
 
 
 
 
 
 
..Rash (specify location and brief 
description): 
 
 
 
 
 
 
 
 
 
..Other illness or symptoms (specify): 
 
 
 
 
 
 
 
 
 
 
If there is any symptom grade ≥ 2, you must notify the supervising medical officer and 
the participant must be evaluated by the medical team.    
 
 
 

APPENDIX 3: PARTICIPANT MONITORING FORM [EXAMPLE] 
Participant ID (Barcode): 
 
 
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Table 2:  Physical Examination 
 
You must complete this table for any participant reporting any bolded symptom in Table 1 
OR for any symptom grade ≥2  
 
Record the result under the column that corresponds to the day the assessment was 
taken.   
Measurements 
Post-treatment day(s) 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
Height (cm) 
 
 
 
 
 
 
 
Weight (kg) 
 
 
 
 
 
 
 
BMI (calculated) 
 
 
 
 
 
 
 
Temperature 
 
 
 
 
 
 
 
Blood pressure, sitting 
 
 
 
 
 
 
 
Blood pressure, lying down (measure only 
if sitting systolic BP <100) 
 
 
 
 
 
 
 
Post-Exam Adverse Event Grade (Assign grade of 0-5 for the adverse reactions below based 
on physical exam. See Appendix 4 under “post-exam assessment” for specific grading criteria) 
Allergic reaction 
 
 
 
 
 
 
 
Hypotension (low blood pressure) 
 
 
 
 
 
 
 
Lymphangitis (streaks of redness, 
warmth, and swelling in arms or legs) 
 
 
 
 
 
 
 
 
 

 
 
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APPENDIX 4:  
GUIDE TO ASSIGNING ADVERSE EVENT SEVERITY 
 (Grade 0 = no symptoms; grade 5 = death from adverse event) 
Symptoms/Signs 
Grades 
1. Mild 
2. Moderate 
3. Severe 
4. Life-threatening 
Fever (non-axillary 
temperatures only) 
38.0 – 39.0ºC 
39.1 – 40.0ºC 
> 40.0ºC 
> 40.0ºC for > 48 hrs 
Dizziness, 
giddiness, or 
fainting 
Mild, not 
interfering with 
work or school 
Moderate, 
unable to work 
or attend school 
for 1 day, but 
no fainting 
Any loss of 
consciousness 
(fainting) 
- 
Confusion or 
excess drowsiness* 
Mild, not 
interfering with 
work or school 
Moderate; 
confusion or 
drowsiness 
interfering with 
ability to work 
Confusion, loss 
of memory, or 
sleepiness 
interfering with 
activities of daily 
living 
Delerium, inability 
rouse, or coma  
Fatigue 
Mild, not 
interfering with 
work or school 
Moderate, 
unable to work 
or attend school  
at least 1 day 
Unable to 
perform 
activities of daily 
living, > 1day 
Required 
hospitalization 
Headache 
Mild pain not 
interfering with 
work or school 
Moderate pain; 
pain or 
analgesics 
interfering with 
ability to work 
or attend school 
Severe pain; 
pain or 
analgesics 
interfering with 
activities of daily 
living 
Disabling, duration > 
48 hr 
Cough 
Mild, relieved 
by non-
prescription 
medication 
Requiring 
narcotic 
antitussive 
Severe cough or 
coughing 
spasms, poorly 
controlled by 
treatment 
Hospitalization or 
respiratory failure 
requiring mechanical 
ventilation 
Difficulty breathing 
(wheezing or 
dyspnea) 
Mild, not 
interfering with 
work or school 
Moderate, 
unable to work 
or attend school 
for 1 day 
Severe, more 
than 1 day and 
required transfer 
to clinic or 
hospital 
Hospitalization or 
respiratory failure 
requiring mechanical 
ventilation 
Nausea 
Able to eat 
Oral intake 
significantly 
decreased 
No significant 
intake, requiring 
IV fluids 
- 
Vomiting 
1 episode in 24 
hours over 
pretreatment 
2-5 episodes in 
24 hours over 
pretreatment 
≥ 6 episodes in 
24hours,  or 
need for IV 
fluids 
(0upatient) 
Hemodynamic 
collapse or overnight 
hospitalization 

Appendix 4: GUIDE TO ASSIGNING ADVERSE EVENT SEVERITY 
 (Grade 0 = no symptoms; grade 5 = death from adverse event) 
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Protocol version date: 05 July 2017 
 
Symptoms/Signs 
Grades 
1. Mild 
2. Moderate 
3. Severe 
4. Life-threatening 
Diarrhea 
Increase of < 4 
stools/day over 
pre-treatment 
Increase of 4-6 
stools/ day, or 
nocturnal stools 
Increase of ≥ 7 
stools/ day or 
need for 
outpatient 
parenteral 
support for 
dehydration 
Physiologic 
consequences wth 
hemodynamic 
collapse or requiring 
hospitalization 
Abdominal pain 
Mild pain not 
interfering with 
work or school 
Moderate pain; 
pain or 
analgesics 
interfering with 
ability to work 
or attend school 
Severe pain; 
pain or 
analgesics 
interfering with 
activities of daily 
living 
Disabling, duration > 
48 hr 
Unusual swelling 
(beyond baseline 
lymphedema) 
Mild, not 
interfering with 
work or school 
Moderate, 
unable to work 
or attend school 
1 day  
Severe, unable 
to work/school 
>1 day 
Severe, limiting 
activities of daily living 
(unable to walk) > 2 
days 
Joint or muscle pain 
Mild pain not 
interfering with 
work or school 
Moderate pain; 
pain or 
analgesics 
interfering with 
ability to work 
or attend school 
Severe pain; 
pain or 
analgesics 
interfering with 
activities of daily 
living 
Disabling, duration > 
48 hr 
Swelling or pain in 
your armpit or 
groin* 
Mild, not 
interfering with 
work or school 
Moderate, 
unable to work 
or attend school 
1 day  
Severe, unable 
to work/school 
>1 day 
Severe, limiting 
activities of daily living 
(unable to walk) > 2 
days 
Men only:  testicular 
or scrotal pain 
Mild, not 
interfering with 
work or school 
Moderate, 
unable to work 
or attend school 
1 day  
Severe, unable 
to work/school 
>1 day 
Severe, limiting 
activities of daily living 
(unable to walk) > 2 
days 
Itching skin 
Mild, not 
interfering with 
work or school 
Moderate, 
unable to work 
or attend school 
1 day  
Severe, unable 
to work/school 
>1 day 
 
Rash 
 
 
Localized rash 
(covers only 
one part of the 
body) 
Diffuse rash 
(covers multiple 
parts of the 
body)  
Diffuse rash 
(covers multiple 
parts of the 
body) AND has 
any blisters or 
ulcers or mouth 
sores 
Extensive areas with 
blisters or ulcers OR 
peeling or blackening 
of skin 
Other illness or 
symptoms  
 
 
Mild, not 
interfering with 
work or school 
Moderate, 
unable to work 
or attend school  
at least 1 day 
Unable to 
perform 
activities of daily 
living, > 1day 
Required 
hospitalization 
 
Post-Exam 
Assessment 
Grades 
1. Mild 
2. Moderate 
3. Severe 
4. Life-threatening 

Appendix 4: GUIDE TO ASSIGNING ADVERSE EVENT SEVERITY 
 (Grade 0 = no symptoms; grade 5 = death from adverse event) 
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Acute allergic 
reaction 
Transient rash, 
drug 
Fever <38ºC 
(<100.4ºF) 
Urticaria, drug 
fever ≥38ºC 
(≥100.4ºF) 
and/or 
asymptomatic 
bronchospasm 
Symptomatic 
bronchospasm, 
requiring 
parenteral 
medication(s) 
with or without 
urticaria 
Anaphylaxis with 
hypotension required 
hospitalization 
Hypotension (low 
blood pressure) 
Changes, but 
not requiring 
therapy 
(including 
transient 
orthostatic 
hypotension) 
Requiring brief 
fluid 
replacement 
(such as oral 
rehydration) but 
not 
hospitalization 
Requiring i.v. 
fluids without 
overnight 
hospitalization.  
No sequelae. 
Required overnight 
hospitalization for i.v. 
fluids, or Shock 
(acidemia and 
impaired vital organ 
function due to tissue 
hypoperfusion) 
Lymphangitis 
Mild, not 
interfering with 
work or school 
Moderate, 
unable to work 
or attend school 
1 day  
Severe, unable 
to work/school 
>1 day 
Severe, limiting 
activities of daily living 
(unable to walk) > 2 
days 
 
Note on general aspects of grading 
0 = No adverse event or within normal limits 
1 = Mild adverse event, does not interfere with work or school 
2 = Moderate adverse event, interferes with work or school at least 1 day 
3 = Severe and undesirable adverse event; interferes with ADL, requires medical assessment 
4 = Potentially life-threatening or disabling adverse event; requires transfer to medical facility 
5 = Death  
 
Note: Any event ≥ grade 2 requires a medical evaluation and notification of the medical officer. 
Any grade 3, 4 or 5 event or overnight hospitalization requires an Adverse Event Evaluation and 
Report Form. 
 

 
 
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APPENDIX 5: 
ADVERSE EVENT EVALUATION AND REPORT FORM 
(AEERF) [EXAMPLE] 
 
Participant ID (Barcode): 
 
Instructions: Complete this form AFTER completing the Participant Monitoring Form for 
anyone with symptoms or signs of grade 3 or higher (unable to perform activities of daily 
living without assistance for at least one day). The purpose of this form is to provide additional 
information on more severe adverse events and to assist the medical officer in determining 
whether a Serious Adverse Event (SAE) has occurred. Please refer to Appendix 5a for 
definitions.  
 
Clinician (required): 
 
1. PARTICIPANT INFORMATION 
Participant ID (Barcode): 
 
Gender:   ☐M    ☐F 
Age:_____Years 
Weight:_____Kg 
Height:_____cm 
Village of Residence: 
 
2. MDA TREATMENT 
Treatment Date (DD-MM-YYY)___________ 
Treatment Village:______________________ 
Anything irregular about treatment? 
☐No   ☐Yes (specify): 
Medications received 
 Albendazole  (dose:____mg) 
 DEC 
 
(dose:____mg) 
 Ivermectin 
(dose:____mg) 
Was this the first time you have ever been treated with one of the MDA medications? If 
No, explain when and circumstances of prior treatment.  
 
Albendazole ☐Yes ☐No (explain): 
DEC 
 
☐Yes ☐No (explain): 
Ivermectin 
☐Yes ☐No (explain): 
 
3. OTHER MEDICATIONS AT TIME OF MDA  
Please include prescription and non-prescription medications/supplements/herbal remedies 
taken within 5 days of the MDA.  DO NOT include medications used to treat the SAE. 
Medication 
Indication 
Dose and 
Frequency 
Days on which each medication was taken, relative to 
MDA (if taken the day of MDA, mark “0”; the day 
before, mark “-1”; the day after, “+1”, and so forth.) 
 
 
 
-5   -4   -3   -2   -1   0   +1   +2   +3   +4   +5  uncertain 
 
 
 
-5   -4   -3   -2   -1   0   +1   +2   +3   +4   +5  uncertain 
 
 
 
-5   -4   -3   -2   -1   0   +1   +2   +3   +4   +5  uncertain 

Appendix 5: ADVERSE EVENT EVALUATION AND REPORT FORM 
(AEERF) (EXAMPLE) 
 
Participant ID (Barcode): 
 
 
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Protocol version date: 05 July 2017 
 
Medication 
Indication 
Dose and 
Frequency 
Days on which each medication was taken, relative to 
MDA (if taken the day of MDA, mark “0”; the day 
before, mark “-1”; the day after, “+1”, and so forth.) 
 
 
 
-5   -4   -3   -2   -1   0   +1   +2   +3   +4   +5  uncertain 
 
4. DESCRIPTION OF THE ADVERSE EVENT 
Date of onset (DD-MM-YYYY): 
How long after drugs were taken did the 
event begin? 
_____hours  OR _____days 
Clinical signs and symptoms (please describe) 
 
 
 
 
 
Do you (the clinician) think this adverse event is/was life-threatening? 
☐Yes  
☐No  
Was the participant hospitalized? 
 
☐Yes  
☐No  
If yes, indicate 
1. Date of admission (DD-MM-YYYY): 
 
2. Reason for admission: 
 
3. Date of discharge (DD-MM-YYYY): 
 
4. Clinical course, including drug treatments given to treat adverse event: 
 
 
 
 
 
Attach a copy of any medical records relating to the diagnosis and treatment of the adverse 
event 
Laboratory results and diagnostic tests (indicate date, test name, and results): 
 
 
 
 
 
 
 

Appendix 5: ADVERSE EVENT EVALUATION AND REPORT FORM 
(AEERF) (EXAMPLE) 
 
Participant ID (Barcode): 
 
 
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5. ADVERSE EVENT OUTCOME (Check only ONE) 
☐Recovering/resolving 
 
 
☐Not recovered/not 
resolved 
 
 
☐Recovered/resolved 
Date: (DD-MM-YYY) 
 
☐Recovered/resolved 
with sequelae 
Date:(DD-MM-YYY) 
Sequelae: 
☐Unknown 
☐Fatal 
(death) 
 
Date:(DD-MM-YYY) 
 
Autopsy: ☐Not done   ☐Done (provide report)   ☐Planned     ☐ Status Unknown 
 
Death certificate: ☐Provided   ☐Requested   ☐Not available   ☐ Status Unknown 

Appendix 5: ADVERSE EVENT EVALUATION AND REPORT FORM 
(AEERF) (EXAMPLE) 
 
Participant ID (Barcode): 
 
 
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6. CONCLUSIONS (to be completed by the health-care provider) 
Presumptive diagnosis: 
 
Do you think this adverse event was caused by the MDA medications? Refer to Appendix 5a  
for detailed explanation of choices. 
 Definitely  
 Probably (explain): 
 Possibly (explain): 
 Unrelated 
If “unrelated”, what do you believe was the cause of the adverse event? 
 
 
Does this event meet the criteria for a Serious Adverse Event (SAE)?  Refer to Appendix 5a for 
detailed definitions of criteria. 
 
 Yes, based on the following criteria 
 Death 
 Life-threatening  
 Hospitalization  
 Disability or permanent damage 
 Other serious important medical event: specify 
 
 No 
 
 
REPORTER INFORMATION AND SIGNATURES 
Investigator Name: 
Investigator Signature:                                 Date:  
Reporter Name: 
Reporter Signature:                                      Date:  
Reporter’s phone number: 
Reporter’s email address: 

 
 
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APPENDIX 5A: REQUIRED REPORTING GUIDELINE FOR SERIOUS 
ADVERSE EVENTS 
Participant ID (Barcode): 
 
An Adverse Event Evaluation and Report Form (AEERF) should be completed for every severe 
adverse event (those scoring grade 3 or higher, see Appendix 4). However, a grade 3 or severe 
adverse event is NOT the same as a Serious Adverse Events (SAE) and the majority of grade 3 
adverse events will not be classified as SAE. The term "severe" is often used to describe the 
intensity (severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the 
event itself, however, may be of relatively minor medical significance (such as severe 
headache). This is not the same as "serious," which is based on patient/event outcome or action 
criteria usually associated with events that pose a threat to a patient's life or functioning. 
Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.  
The AEERF should guide the medical monitor or health care provider evaluating the patient 
experiencing a severe AE to determine whether a SAE has occurred.  All SAE must be reported 
promptly. (See Safety Reporting Plan for SAE Reporting Timeline) 
Required Reporting  
A written report or CRF must be sent from the local physician and local medical monitor by 
email (scanned records) in the stated timeframes to the Country PI, Global Medical Monitor 
including the Project PI for the events listed below.  
Guidelines for Reporting - Standard Reporting Information   
The following information should be included in the initial report/CRF (additional 
information may be requested): 
 

APPENDIX 5A: REQUIRED REPORTING GUIDELINE FOR SERIOUS 
ADVERSE EVENTS 
 
 
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Minimum Criteria for Reporting  
Information for final description and evaluation of a case report may not be 
available within the required time frames for reporting outlined below. Initial 
reports should be submitted within the prescribed time as long as the following 
minimum criteria are met: an identifiable patient; an identifiable reporting 
source; and an event or outcome that can be identified as serious. Follow-up 
information should be actively sought and submitted as it becomes available.  
Complete the following information if available on the initial report and complete a follow-up 
report as new or additional information becomes available as noted below: 
 
Description of the event 
Date, time of onset 
Clinical history 
Associated signs and symptoms 
Temporal association with study agent 
Medical management, including rationale 
Pertinent laboratory tests 
Severity – see definitions or toxicity score 
Causal relationship to the study drug/vaccine 
 
Other information 
Relevant past medical history 
Concomitant medications 
Autopsy report or expectation of an autopsy in the case of death 
 
Outcome of event 
Date, time of resolution, if resolved 
 
Plans for study participant 
Follow-up 
Treatment of event 
Return to treatment/Contraindicate 
 
Location/Study Centre 
 
Reporting Physician 
 
Verification of notification to IRB and Safety Monitor or DSMB 
Definitions 
 
Adverse Event [Experience] (AE): 

APPENDIX 5A: REQUIRED REPORTING GUIDELINE FOR SERIOUS 
ADVERSE EVENTS 
 
 
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Any untoward medical occurrence, including dosing errors, that may arise during 
administration of study agent, and which may or may not have a causal relationship with 
the study agent. 
 
Unexpected Adverse Event [Experience]: 
Any adverse experience that has not been previously observed (i.e., included in the 
labelling), whether or not the event is anticipated because of the pharmacologic 
properties of the study agent. 
 
Serious Adverse Event (SAE): 
Any adverse event occurring at any dose that results in any of the following outcomes: 
a. Death 
b. Life threatening – defined as an experience that places the patient or participant, in 
the view of the Investigator, at immediate risk of death from the reaction as it 
occurred.  (Note; this does not include a reaction that, had it occurred in a more 
severe form, might have caused death.) 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
d. Results in a congenital anomaly or birth defect 
e. Results in a persistent or significant disability or incapacity 
f. Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or participant and 
may require medical or surgical intervention to prevent one of the outcomes listed in 
this definition.  (The event might be defined as serious based on progression of 
grade if Toxicity Tables are being used.) 
Severity  
Adverse experience/events should be assessed by the on-site investigator as to their 
severity and/or intensity. 
a. Life threatening 
b. Severe: incapacitating with inability to work or do usual activity 
c. Moderate: enough discomfort to cause interference with usual activity 

APPENDIX 5A: REQUIRED REPORTING GUIDELINE FOR SERIOUS 
ADVERSE EVENTS 
 
 
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d. Mild: awareness of sign or symptom, but easily tolerated 
Relationship or Association with Use of Study Agent or Participation in the Study 
Causal relationship with the investigational study treatment must be assessed by the on-site 
investigator using the following or similar terms: 
 
Definite – clear-cut temporal association, with a positive re-challenge test or laboratory 
confirmation. 
 
Probable – clear-cut temporal association, with improvement upon drug withdrawal, and 
not reasonably explained by the participant’s known clinical state. 
 
Possible – less clear temporal association; other aetiologies are possible. 
 
None – no temporal association with the study drug; related to other aetiologies such as 
concomitant medications or conditions, or participant’s known clinical state. 
Other Reporting 
Investigators are reminded that they may have other reporting obligations: 
 
For all studies, there must be compliance with the clinical site Ethics/IRB’s policy for 
reporting adverse events. (As soon as possible for SAEs and as required for AEs.) 
 

 
 
Protocol version: 2.2 
 
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APPENDIX 6A: INFORMATION SHEET AND INFORMED CONSENT 
FORM (VERSION 1.2, 22 AUGUST 20116) 
Participant ID (Barcode): 
 
Project Title: Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic 
Filariasis in Haiti 
Part A - Information Sheet (Adult) 
Lymphatic filariasis (LF) is a disease carried by mosquitoes and caused by tiny worms in the 
blood. In Haiti we sometimes call it maladi filarioz. It can cause complications like swelling of the 
legs (lymphedema) or the scrotum (hydrocele).  The Haitian Ministry of Public Health and 
Population (MSPP) has given treatment for these worms every year in order to stop LF in Haiti.  
Though treatment has been given annually since 2001, too many people are still infected with 
LF in your community.  
In this consent form the term “you” may refer to you or your child. You are being asked to take 
part in this study because you live in an area where you may become sick with lymphatic 
filariasis. You are being asked to consent for yourself and/or your child or children 
Why is this Study being done? 
This study is being conducted by the Ministry of Public Health and Population (MSPP). We are 
currently investigating a new combination of three drugs to treat LF. In studies in other 
countries, this new combination has been shown to be more effective in killing the LF worms 
more rapidly than the usual combination of two drugs you take for LF annually. It could 
accelerate the elimination of LF in Haiti and in your community.  It consists of the usual drugs 
you take for LF (diethylcarbamazine and albendazole) plus another drug called ivermectin.  This 
study is done to learn about the side effects people may have when they take these different 
drugs together to get rid of the LF worm. 
As part of this study you will either take the standard combination of two drugs including 
diethylcarbamazine (DEC) and albendazole (ALB) or the combination of three drugs including 
diethylcarbamazine (DEC), albendazole (ALB) and ivermectin (IVM). You will be asked to 
swallow pills; the number of pills will be calculated based on your body weight. When you take 
these drugs your body may react to the dying worms by developing a fever. You may also feel 
tired or have body aches for one or two days.  This means that the drugs are killing worms.   We 
want to collect information about how your body reacts to these medications, and if taking the 
three drugs together causes your body to react more strongly compared to when you take the 

 
Protocol version: 2.2 
 
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two drugs. Finally, we want to know if taking three drugs instead of two will completely eliminate 
the LF worms from your body if you are infected.  
How many people will take part in the study? 
Approximatively 6,000 men, women and children will take part in this study in Haiti and about 
10,000 total in all countries involved 
What is involved in the study?  
Half of the people who will accept to participate in the study will get 2 drugs (DEC + ALB) and 
the other half will get 3 drugs (DEC + ALB+ IVM).   You will be assigned to either treatment 
group.  Before you receive any medication we will ask you few questions about your health. We 
might also take your blood pressure and temperature. We will also take few drops of blood by 
pricking your finger to see if you are infected with LF using a rapid test.   If the rapid test is 
positive we will ask you if we can visit you at night (between 10 pm and 12 am) to get another 
drop of blood to measure how many worms are in your blood.   Even if the rapid test is negative 
you will be treated with drugs because the test can be negative if the infection is very light. 
Some members of the study team will follow up with you 1 and 2 days after you took the drugs.  
During these visits the study team will ask how you are feeling and might take your temperature 
and blood pressures.  The study team will be in your village 3 to 7 days after you took the drug 
to make sure you are still feeling well.  If you are not well, then you will be examined.  If your 
illness is severe then the study team will have you see a doctor who can provide treatment. The 
study team will record information about how you are feeling at each visit.    
If you tested positive for LF at the beginning of the study, the study team will again collect a 
small amount of blood from your finger 12 months after you took the medication.  If you still 
have LF, you will be treated again with the standard treatment for LF in Haiti (2 drugs). So in 
total, you will be in this study for one year.  After we have finished distributing the drugs for LF, 
will ask some of you about how you felt about the study. 
What are the risks of the study? 
The risk of drawing blood from a finger prick is minimal, although some people become dizzy. 
You may experience momentary discomfort and/or bruising. Children may be uncomfortable 
and cry when blood is drawn. You will be watched by members of the research team and be 
given the opportunity to rest if you feel dizzy. Excess bleeding or infection may occur after a 
finger prick. The study personnel are trained in sterile techniques, so this chance is very small.  
When you take the drugs your body may react to the dying worms by developing a fever. You 
may also feel tired or have body aches for one or two days.  This means that the drugs are 
killing worms.   Other possible effects are an upset stomach such as nausea after ingesting the 

 
Protocol version: 2.2 
 
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tablet, dizziness and occasionally itchy skin.  If you experience any of these side effects, you will 
be seen by a medical personnel and refer to a physician if needed. 
Are there benefits to taking part of the study? 
This study will help treat your infection for LF and intestinal worms. The investigators hope that 
the information learned from this study will benefit people in Haiti as well as in other areas of the 
world affected by LF.  From this work it may be possible to reduce the number of MDA (mass 
drug administration) treatments needed to eliminate this problem in Haiti. 
Is the participation in this study voluntary? 
You are free to choose to be in this study or not. Taking part of the study is voluntary.  If you 
decide not to be in this study, you and your family will not lose any benefits.  You may still be 
treated at the Community Health Center.  If you agree to participate in this study, you may stop 
your participation at any time without any penalty. If you leave the study and the blood test 
shows that you are infected with LF, you will be referred to the local health center and be 
treated according to the standard treatment for LF in Haiti (2 drugs, DEC and ALB).  
Are you going to share information you collected about me with other persons? 
Only the people involved in this study will have access to the information collected in this study.  
Any information will be kept private as allowed by law.  Your name will not appear in any report 
that comes from this survey.  Your blood sample will not have any identifying information about 
you on it. We will share the test results obtained as part of the study with the local health worker 
at the health center only if you approve.   
What if I become sick as a result of the study? 
If you experience physical injury or illness as a result of participating in this study, medical care 
will be available at the local health center or the hospital. You will be transported to the 
Departmental Hospital if your symptoms are more severe.  If your illness is determined to be 
related to taking the drugs for LF, we will cover all the medical costs. 
What are you going to do with the samples of blood you collect? 
A little more blood could be collected to be saved and stored in a freezer and send to the United 
States. Your blood may be used for future testing for LF or for other diseases that might affect 
the health of your community. Your blood will NOT be tested for HIV. We will not perform human 
genetic testing on your blood. Stored samples will be labelled with a code only and not linked to 
your name. Stored samples will only be used with approval from an Ethical Committee. You will 
not be contacted for additional consent. You may still participate in this study if you do not 

 
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consent to give additional blood for future scientific studies about diseases affecting your 
community. 
How much does it cost to participate to the study? 
There is no cost to you to participate in this study. You will receive no payment for taking part in 
this study. All study drugs and laboratory tests are free. 
You are free to contact the following person for any details and clarifications: 
Dr. Jean Frantz Lemoine, MD, MPH,  
Coordonnateur de Programmes Nationaus de la Malaria et de la Filariose Lymphatique 
Tel: (509) 3744-8755 or (509) 3946-3026 
 
 

 
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Project Title: Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic 
Filariasis in Haiti  
Part B : Information Sheet (children 7–17 year old, if a parent accepted that the child 
participates to the study) 
We want to ask you to participate in a research study. We are currently investigating a new 
combination of three drugs against a disease called lymphatic filariasis (LF). LF is a disease 
carried by mosquitoes and caused by tiny worms in the blood. In Haiti we sometimes call it 
maladi filarioz. It can cause complications like swelling of the legs (lymphedema) or the scrotum 
(hydrocele).  This new combination has been shown in other studies to be more effective in 
treating LF than the usual combination of two drugs (diethylcarbamazine and albendazole). The 
new combination consists of the usual drugs you take for LF (diethylcarbamazine and 
albendazole) plus another new drug to Haiti called ivermectin.  This study is done to learn 
whether people feel worse if they have taken the three drugs together to get rid of the LF 
parasite. 
  
If you accept to participate, we will ask you few questions about your health. It is possible that a 
nurse examine you briefly. We will also take some drops of blood from your finger tip to test for 
LF. Finally, we will ask you to swallow some tablets that treat LF.  In total, it will take about 30 
minutes of your time.  
 
We will visit you several times in the 7 days after you have taken the tablets. During the first two 
days after you have taken the tables we will ask you how you feel. If you feel sick, we will ask 
you few more questions and we will examine you. During the next 5 following days, we will 
make sure that you still feel ok. If you feel sick, you will be examined by a nurse or a doctor. 
When we prick your finger, it is possible that you will be afraid or that it will be a little painful. 
When you take the drugs your body may react to the dying worms by developing a fever. You 
may also feel tired or have body aches for one or two days.  This means that the drugs are 
killing worms.   Other possible effects are an upset stomach such as nausea after ingesting the 
tablet, dizziness and occasionally itchy skin.  If you experience any of these side effects, you will 
be seen by a medical personnel and refer to a physician if needed. 
You can refuse to participate to the study. It is not a problem at all. You can also change your 
mind during the study and stop to participate. 
 
If you have questions, you can ask your Mom and Dad. You can also ask questions to any of 
the research team members. Do you have any questions?  
 
You Dad and Mom accepted that you participate to the study. Do you accept to participate to 
the study? 
 
 

 
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Protocol version date: 05 July 2017 
 
Project Title: Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic 
Filariasis in Haiti  
Part C (Consent for adults) 
Written Informed Consent Form for Participation in the Study (Adult ≥18 year old) 
I have read or somebody has read to me the information included in the information sheet, and I 
fully understood the details. I have also been explained by the Principal Investigator or his duly 
authorized representative the full details. Having fully satisfied myself with the explanation 
given, of my own decision with full sense / awareness, give my consent for all screening 
procedures that are required for screening for infection due to LF. Also I give my consent for 
being treated with the assigned (2- or 3-drug combination) drugs for clearing infection.  
I am also fully aware of my right to withdraw myself from the study, and in case should I stop 
participating, that I will be given treatment for the disease or will be referred for appropriate 
treatment. 
 
Given this day  
 
in the month of  
 
 
in the year 
 
 
Signed in my presence. 
 
 
 
 
 
Name of the individual:  
 
 
 
 
 
 
Signature of the individual:   
 
 
 
 
 
Name of the witness:   
 
 
 
 
 
Signature of the witness:  
 
 
 
 
 
 
Address 1:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Address 2:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of the informant:  
 
 
 
 
 
 
 
 
 
 
Signature of the informant:  
 
 
 
 
 
 
 
 
 
Finger print of 
individual if 
informed 
consent signed 
by witness 

 
Protocol version: 2.2 
 
Page 62 of 67 
Protocol version date: 05 July 2017 
 
Project Title: Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic 
Filariasis in Haiti. 
Part D (Consent for children) 
Written Consent Form for Children (less than 18 year old) Participating in the Study 
I have read or somebody has read to me the information included in the information sheet, and I 
fully understood the details. I have also been explained by the Principal Investigator or his duly 
authorized representative the full details, and having fully satisfied myself with the explanation 
given, of my own decision with full sense / awareness, give my consent for / my son / my 
daughter for all screening procedures that are required for screening for infection due to 
filariasis. Also I give my consent that my child will be treated with the assigned (2- or 3-drug 
combination) drugs for clearing infection. I am also fully aware of my right to withdraw my ward 
from the study, and in case should I stop my child participating, that my ward will be given 
treatment for the disease or will be referred for appropriate treatment. 
Given this day  
 
in the month of  
 
 
in the year 
 
 
Signed in my presence. 
 
 
 
 
 
Name of the parent/guardian:  
 
 
 
 
 
Signature of the parent/guardian:  
 
 
 
 
 
Name of the child:  
 
 
 
 
 
 
 
Name of the witness:   
 
 
 
 
 
 
Signature of the witness:  
 
 
 
 
 
 
Address 1:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Address 2:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of the informant:  
 
 
 
 
 
 
 
 
 
 
Signature of the informant:  
 
 
 
 
 
 
 
 
 
Finger print of 
parent/guardian 
if informed 
consent signed 
by witness 

 
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Protocol version date: 05 July 2017 
 
Project Title: Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic 
Filariasis in Haiti. 
Part E (Assent) 
Assent for children 7–17 years old (only if a parent has accepted that the child 
participates) 
 
I have read or somebody has read to me the information included in the information sheet, and I 
fully understood the details. The Principal Investigator or his/her representative also explained 
to me the details of the study. I am satisfied with the explanation that was given to me. I agree 
to participate to the study.   
 
Given this day  
 
in the month of  
 
 
in the year 
 
 
Signed in my presence. 
 
Name of the individual:  
 
 
 
 
 
 
 
Signature of the individual:   
 
 
 
 
 
 
Name of the witness:   
 
 
 
 
 
 
Signature of the witness:  
 
 
 
 
 
 
 
 
 
Address 1:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Address 2:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of the informant:  
 
 
 
 
 
 
 
 
 
 
Signature of the informant:  
 
 
 
 
 
 
 
 
 
 
 
 
Finger print of 
individual if 
informed 
consent signed 
by witness 

 
Protocol version: 2.2 
 
Page 64 of 67 
Protocol version date: 05 July 2017 
 
 
Project title: Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) 
versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic 
Filariasis in Haiti. 
Part F (Blood storage) 
Consent for Future use of Participant’s Blood 
I have read or somebody has read to me the information included in the information sheet, and 
fully understood the details. I have also been explained by the Principal Investigator or his duly 
authorized representative the full details, and having fully satisfied myself with the explanation 
given, of my own decision with full sense / awareness, give my consent for my blood or the 
blood of my son / my daughter for storage and additional testing in the future.  
Given this day  
 
in the month of  
 
 
in the year 
 
 
Signed in my presence. 
 
Name of the individual or parent/guardian:   
 
 
 
 
Signature of the individual or parent/guardian:  
 
 
 
 
Name of the child if less than 18 year old:   
 
 
 
 
Name of the witness:   
 
 
 
 
 
Signature of the witness:  
 
 
 
 
 
 
Address 1:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Address 2:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of the informant:  
 
 
 
 
 
 
 
 
 
 
Signature of the informant:  
 
 
 
 
 
 
 
 
 
Finger print of 
individual if 
informed 
consent signed 
by witness 

 
 
Protocol version: 2.2 
 
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Protocol version date: 05 July 2017 
APPENDIX 6B: INFORMED RE-CONSENT FORM (V.1, 30 MAY 2017) 
STUDY NAME: Community Based Safety Study of 2-drug (Diethylcarbamazine and 
Albendazole) versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for 
Lymphatic Filariasis in Haiti 
 
PRINICIPLE INVESTIGATORS: Dr. Jean Frantz Lemoine and Dr. Christine Dubray 
 
Approximately one year ago, you volunteered to be a part of a research study about lymphatic 
filariasis, which is caused by worms that live in your blood. You may also hear people calling 
this disease malady filarioz. 
 
A year ago, researchers from the Ministry of Public Health and Population explained to you the 
reasons of the study. You received the study medicine after you agreed to be in the study.  The 
study team told you that they would come back one year later to see how well the medicine had 
killed the worms in your blood.  This is the reason why we are visiting you today. 
 
Today, we are asking you to accept to continue to participate in the study to see how well the 
medicines you took a year ago killed the worms. If you agree, you will be tested for malady 
filarioz with the tests listed in the table below. If we find worms in your blood, we will give you 
medicine to treat the worms free of charge. If you are pregnant, we cannot treat you because 
we do not know if the medicine is safe for the baby. If we found worms in your blood, we advise 
that after the delivery you participate to the community treatment for malady filarioz.  
 
Type of Test 
What Will Happen 
Filaria Test Strip &  
Thick Blood Smear 
We will take a small amount of blood from your finger. It will only take a few 
minutes. The blood collection might cause some pain. Infection and bleeding 
may also occur, but this is very unlikely to happen. We will test your blood to 
see if you have worms in your blood.  
Dried Blood Spot 
Some of your blood will be kept on filter paper and tested for malady filarioz as 
well. We may also test the blood for other infections. The blood may be stored 
even after this study ends. The blood may be sent to the United States. The 
blood will not be tested for HIV and it will not be used for genetic testing. 
 
We may use your test results in another study that would evaluate how many people in your 
community have malady filarioz. 
 
You will not be charged to be in the study. You will not receive any gifts or money to be in the 
study. If you are injured or if you get sick because of the study, we will pay for your care.  
 
Your participation is voluntary. You will not be penalized if you do not want to volunteer. The 
worms can still be treated during the government’s regular community mass drug administration 
for malady filarioz.  You may stop your participation in the study at any time and you do not 

APPENDIX 6B: INFORMED RE-CONSENT FORM (V.1, 30 MAY 2017) 
Protocol version: 2.2 
 
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Protocol version date: 05 July 2017 
 
have to give a reason. If you stop to be in the study, you will not be charged for any of the 
medicines you took. 
 
We will keep your name and information about you private. Only members of the study team will 
have access to the information. A code using only numbers will be used to identify your blood 
samples. We will keep your information secret even if you decide to stop your participation in 
the study. 
 
 
If you have questions about your participation in this study, you may call Dr. Jean Frantz 
Lemoine, MD, MPH, Coordonnateur des Programmes Nationaux de la Malaria et de la Filariose 
Lymphatique Tel: (509) 3744-8755 or (509) 3946-3026 
 
By signing this page, you confirm that you and/or your children have voluntarily agreed to be in 
this study. 
Participant’s name: 
 
Consent date: 
 
(For participant aged 7–17 years old, please fill out the 
assent form) 
Signature/thumbprint 
 
 
 
 
Witness’ name: 
 
Date: 
 
Signature 
Informant’s name: 
 
Date: 
 
Signature 
 
ASSENT FORM (To be signed for all children who are 7–17 years old) 
 
My name is ________________________________________________________ 
My parent’s/legal guardian name is: _____________________________________  
I agree that I am volunteering to be in this study and that my parents/legal guardian agree that I 
can participate. I understand that I will have my blood drawn and tested and that I might receive 
medicine if we find worms in my blood. I also understand that I may decide to quit the study at 
any time.  
Participant’s name: 
 
Consent giver’s name: 
Signature/thumbprint 

APPENDIX 6B: INFORMED RE-CONSENT FORM (V.1, 30 MAY 2017) 
Protocol version: 2.2 
 
Page 67 of 67 
Protocol version date: 05 July 2017 
 
 
Relation to participant: 
(Parent/ Legal guardian)