Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R01HL134211 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
Not provided
Not provided
Not provided
This is a randomized, three-arm, open-label, clinical trial of malaria chemoprevention in children with sickle-cell anemia (SCA) at a single site in Homa Bay, Kenya. The study will enroll 246 children under 10 years of age, randomize participants 1:1:1 to one of three malaria chemoprevention regimens, and follow participants monthly for 12 months in order to record clinical episodes of malaria or SCA-related morbidity. Analyses will compare the efficacy of each regimen to prevent malaria and SCA morbidity.
Purpose of the study:
Primary Objective: To compare the efficacy of daily proguanil with monthly sulfadoxine/pyrimethanine-amodiaquine (SP-AQ) and with monthly dihydroartemisinin-piperaquine (DP) on the incidence of falciparum malaria in children with SCA.
Secondary Objective: To compare the efficacy of these malaria chemoprevention strategies on the incidence of major complications of SCA.
Background & significance
Over 240,000 children with sickle cell anemia (SCA) are born in Africa annually. This number will increase to over 350,000 annual births of children with SCA by the year 2050. Without sophisticated medical care, SCA patients in African settings die at young ages: in a Western Kenya cohort of newborns, 25% of SCA children died before their 3rd birthday. Caring effectively for these children will be a major challenge for developing medical and public health systems in Africa including Kenya, and modeling studies suggest that the adequate provision of effective preventive care can substantially reduce the mortality of these children. Preventive care for SCA children must be evidence-based and tailored to the unique epidemiology of comorbidities in African settings.
Children under 5 years of age in sub-Saharan Africa also suffer the majority of the annual 350 million infections and 500,000 deaths globally. Reducing this burden is a global public health priority, particularly in areas of high transmission like Western Kenya. In the absence of an effective vaccine, global malaria control requires effective treatments and a suite of preventive measures that act upon the parasite, environment, and host. Among these preventive strategies is the administration of prophylactic antimalarials to high risk groups, including pregnant women, infants, and children exposed to seasonal malaria transmission. In these high-risk groups malaria morbidity is substantially reduced by routine periodic intake of effective antimalarials.
Children with SCA are at high risk of life-threatening malaria. In East Africa children with SCA admitted to the hospital with malaria parasites were more likely to die than those without parasites. Malaria is also a precipitant of sickle-cell pain crises, by unclear mechanisms. It remains unclear how SCA influences the overall risk of malaria, because most studies have been hospital based and therefore unsuited to capture mild episodes. The twin observations that malaria is more severe in SCA children and precipitates painful crises in these children indicate that the prevention of P. falciparum infections is critical to prolong the survival of SCA children in malaria-endemic areas.
Design & procedures - This is a randomized, three-arm, open-label, clinical trial of malaria chemoprevention in children with sickle-cell anemia (SCA) at a single site in Homa Bay, Kenya. The study will enroll 246 children under 10 years of age, randomize participants 1:1:1 to one of three malaria chemoprevention regimens, and follow participants monthly for 12 months in order to record clinical episodes of malaria or SCA-related morbidity. Analyses will compare the efficacy of each regimen to prevent malaria and SCA morbidity.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Proguanil Oral Tablet | Active Comparator | Proguanil is the current standard of care for chemoprevention of malaria in children with SCA in Kenya. This medication will be taken on a daily basis |
|
| Sulfadoxine/Pyrimethanine-Amodiaquine | Active Comparator | Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) is a combination therapy comprised of sulfadoxine and pyrimethamine (two antifolate antimicrobials) co-administered with amodiaquine. This medication is taken on a monthly basis. |
|
| Dihydroartemisinin-Piperaquine (DP) | Active Comparator | DP is an artemisinin-combination therapy consisting of the artemisinin derivative dihydroartemisinin and the bisquinoline piperaquine. This medication is taken on a monthly basis. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Proguanil Oral Tablet | Drug | Dosing of daily proguanil will be approximately 3mg/kg/day, |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Clinical Malaria Per Patient Year | The primary endpoint is the cumulative incidence of clinical malaria expressed as episodes per person-year at risk. Time at risk will begin when study participants are randomized and receive study drug (i.e. begin chemoprevention) and end when participants reach the end of the observation period. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Severe Anemia | E.g., hemoglobin <5.5 g/dL | 12 months |
| Number of Participants With Severe Malaria | Positive rapid diagnostic test (RDT). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Homa Bay County Referral Hospital | Homa Bay Town | Homa Bay County | 40300 | Kenya |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36215323 | Derived | Taylor SM, Korwa S, Wu A, Green CL, Freedman B, Clapp S, Kirui JK, O'Meara WP, Njuguna FM. Monthly sulfadoxine/pyrimethamine-amodiaquine or dihydroartemisinin-piperaquine as malaria chemoprevention in young Kenyan children with sickle cell anemia: A randomized controlled trial. PLoS Med. 2022 Oct 10;19(10):e1004104. doi: 10.1371/journal.pmed.1004104. eCollection 2022 Oct. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Potential participants will be screened for inclusion in the existing pediatric. Currently, SCA patients are cared for in two parallel clinics: 1) the pediatric medical officer staffs a weekly SCA clinic, and 2) the AMPATH HematoOncology outreach team staffs a monthly 2-day SCA clinic at HBCH.
Potential participants will be screened for eligibility. If they meet all inclusion criteria and do not meet any exclusion criteria, they will be offered enrollment following informed consent.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Proguanil Oral Tablet | Proguanil is the current standard of care for chemoprevention of malaria in children with SCA in Kenya. This medication will be taken on a daily basis Proguanil Oral Tablet: Dosing of daily proguanil will be approximately 3mg/kg/day, |
| FG001 | Sulfadoxine/Pyrimethanine-Amodiaquine | Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) is a combination therapy comprised of sulfadoxine and pyrimethamine (two antifolate antimicrobials) co-administered with amodiaquine. This medication is taken on a monthly basis. Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ): Age 1-5 on Day 1: One tablet 500/25mg SP and one tablet 153mg AQ Day 2 and Day 3: one tablet 153 mg AQ only each day For ages 6-10: Day 1 - 1.5 tablets 500/25mg SP and 1.5 tablets 153mg AQ Days 2 and 3: 1.5 tablets 153mg AQ only each day |
| FG002 | Dihydroartemisinin-Piperaquine (DP) | DP is an artemisinin-combination therapy consisting of the artemisinin derivative dihydroartemisinin and the bisquinoline piperaquine. This medication is taken on a monthly basis. Dihydroartemisinin-Piperaquine (DP): 3) The weight-based dosing of tablets of 40/320mg of DP is described below: Weight (kg) No. of 40/320mg tabs DP daily for 3 days ≤ 5 ¼ 6-10 ½ 11-14 ¾ 15-19 1 20-23 1 ¼ 24-25 1 ½ |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Proguanil Oral Tablet | Proguanil is the current standard of care for chemoprevention of malaria in children with SCA in Kenya. This medication will be taken on a daily basis Proguanil Oral Tablet: Dosing of daily proguanil will be approximately 3mg/kg/day, |
| BG001 | Sulfadoxine/Pyrimethanine-Amodiaquine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of Clinical Malaria Per Patient Year | The primary endpoint is the cumulative incidence of clinical malaria expressed as episodes per person-year at risk. Time at risk will begin when study participants are randomized and receive study drug (i.e. begin chemoprevention) and end when participants reach the end of the observation period. | Posted | Number | episodes/patient year | 12 months |
|
12 months
This protocol collected only SUSARs (Suspected Unexpected Serious Adverse Reactions) and deaths.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Proguanil Oral Tablet | Proguanil is the current standard of care for chemoprevention of malaria in children with SCA in Kenya. This medication will be taken on a daily basis Proguanil Oral Tablet: Dosing of daily proguanil will be approximately 3mg/kg/day, |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Painful Crisis | Blood and lymphatic system disorders | Non-systematic Assessment |
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Steve Taylor | DCRI | 9198245232 | steve.taylor@duke.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 14, 2020 | Apr 26, 2023 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| ID | Term |
|---|---|
| D008288 | Malaria |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D002727 | Proguanil |
| D013413 | Sulfadoxine |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D000096926 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) | Drug | Age 1-5 on Day 1: One tablet 500/25mg SP and one tablet 153mg AQ Day 2 and Day 3: one tablet 153 mg AQ only each day For ages 6-10: Day 1 - 1.5 tablets 500/25mg SP and 1.5 tablets 153mg AQ Days 2 and 3: 1.5 tablets 153mg AQ only each day |
|
| Dihydroartemisinin-Piperaquine (DP) | Drug | 3) The weight-based dosing of tablets of 40/320mg of DP is described below: Weight (kg) No. of 40/320mg tabs DP daily for 3 days ≤ 5 ¼ 6-10 ½ 11-14 ¾ 15-19 1 20-23 1 ¼ 24-25 1 ½ |
|
| 12 months |
| Number of Participants With Hospitalization for Malaria | Patient admitted to hospital for malaria with confirmed positive RDT. | 12 months |
| Number of Participants With Light Microscopy (LM)-Positive Malaria | LM-positive malaria defined as the reported presence of P. falciparum parasites detected by LM irrespective of RDT or other detection results. | 12 months |
| Number of Participants With Unconfirmed Malaria | Defined as the receipt of antimalarials for suspected malaria episodes that were not confirmed by any objective diagnostic test. | 12 months |
| Number of Participants With Fatal Malaria | Defined as death during hospitalization for malaria with positive RDT. | 12 months |
| Number of Participants With Asymptomatic Parasitization | Defined as the presence of parasites during routine follow-up visits as detected by PCR in patients without fever or a history of recent fever. | 12 months |
| Number of Participants With Painful Events | Pain lasting two hours or more without obvious cause. | 12 months |
| Number of Participants With Dactylitis | Pain or tenderness with or without swelling of the hands or feet. | 12 months |
| Number of Participants With Transfusions | Receipt of RBCs (red blood cells) from any caregiver for any indication. | 12 months |
| Number of Participants With Acute Chest Syndrome | Defined as a new pulmonary infiltrate and at least 3 of the following findings: chest pain, temperature elevation > 38.5°C, tachypnea, wheezing, or cough. | 12 months |
| Number of Participants With All-cause Hospitalization | Hospitalization at HBCH or any other inpatient facility with any admitting diagnosis. | 12 months |
| All-cause Deaths | Death by any cause. | 12 months |
| Molecular Markers of Malaria Parasite Drug Resistance | presence of SNPs in parasite genes that confer resistance to the study drugs | 12 months |
Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) is a combination therapy comprised of sulfadoxine and pyrimethamine (two antifolate antimicrobials) co-administered with amodiaquine. This medication is taken on a monthly basis. Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ): Age 1-5 on Day 1: One tablet 500/25mg SP and one tablet 153mg AQ Day 2 and Day 3: one tablet 153 mg AQ only each day For ages 6-10: Day 1 - 1.5 tablets 500/25mg SP and 1.5 tablets 153mg AQ Days 2 and 3: 1.5 tablets 153mg AQ only each day |
| BG002 | Dihydroartemisinin-Piperaquine (DP) | DP is an artemisinin-combination therapy consisting of the artemisinin derivative dihydroartemisinin and the bisquinoline piperaquine. This medication is taken on a monthly basis. Dihydroartemisinin-Piperaquine (DP): 3) The weight-based dosing of tablets of 40/320mg of DP is described below: Weight (kg) No. of 40/320mg tabs DP daily for 3 days ≤ 5 ¼ 6-10 ½ 11-14 ¾ 15-19 1 20-23 1 ¼ 24-25 1 ½ |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) is a combination therapy comprised of sulfadoxine and pyrimethamine (two antifolate antimicrobials) co-administered with amodiaquine. This medication is taken on a monthly basis.
Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ): Age 1-5 on Day 1: One tablet 500/25mg SP and one tablet 153mg AQ Day 2 and Day 3: one tablet 153 mg AQ only each day For ages 6-10: Day 1 - 1.5 tablets 500/25mg SP and 1.5 tablets 153mg AQ Days 2 and 3: 1.5 tablets 153mg AQ only each day
| OG002 | Dihydroartemisinin-Piperaquine (DP) | DP is an artemisinin-combination therapy consisting of the artemisinin derivative dihydroartemisinin and the bisquinoline piperaquine. This medication is taken on a monthly basis. Dihydroartemisinin-Piperaquine (DP): 3) The weight-based dosing of tablets of 40/320mg of DP is described below: Weight (kg) No. of 40/320mg tabs DP daily for 3 days ≤ 5 ¼ 6-10 ½ 11-14 ¾ 15-19 1 20-23 1 ¼ 24-25 1 ½ |
|
|
| Secondary | Number of Participants With Severe Anemia | E.g., hemoglobin <5.5 g/dL | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Severe Malaria | Positive rapid diagnostic test (RDT). | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Hospitalization for Malaria | Patient admitted to hospital for malaria with confirmed positive RDT. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Light Microscopy (LM)-Positive Malaria | LM-positive malaria defined as the reported presence of P. falciparum parasites detected by LM irrespective of RDT or other detection results. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Unconfirmed Malaria | Defined as the receipt of antimalarials for suspected malaria episodes that were not confirmed by any objective diagnostic test. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Fatal Malaria | Defined as death during hospitalization for malaria with positive RDT. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Asymptomatic Parasitization | Defined as the presence of parasites during routine follow-up visits as detected by PCR in patients without fever or a history of recent fever. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Painful Events | Pain lasting two hours or more without obvious cause. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Dactylitis | Pain or tenderness with or without swelling of the hands or feet. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Transfusions | Receipt of RBCs (red blood cells) from any caregiver for any indication. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With Acute Chest Syndrome | Defined as a new pulmonary infiltrate and at least 3 of the following findings: chest pain, temperature elevation > 38.5°C, tachypnea, wheezing, or cough. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Number of Participants With All-cause Hospitalization | Hospitalization at HBCH or any other inpatient facility with any admitting diagnosis. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | All-cause Deaths | Death by any cause. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Molecular Markers of Malaria Parasite Drug Resistance | presence of SNPs in parasite genes that confer resistance to the study drugs | Data not collected. | Posted | 12 months |
|
|
| 2 |
| 81 |
| 22 |
| 81 |
| 0 |
| 0 |
| EG001 | Sulfadoxine/Pyrimethanine-Amodiaquine | Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) is a combination therapy comprised of sulfadoxine and pyrimethamine (two antifolate antimicrobials) co-administered with amodiaquine. This medication is taken on a monthly basis. Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ): Age 1-5 on Day 1: One tablet 500/25mg SP and one tablet 153mg AQ Day 2 and Day 3: one tablet 153 mg AQ only each day For ages 6-10: Day 1 - 1.5 tablets 500/25mg SP and 1.5 tablets 153mg AQ Days 2 and 3: 1.5 tablets 153mg AQ only each day | 7 | 83 | 22 | 83 | 0 | 0 |
| EG002 | Dihydroartemisinin-Piperaquine (DP) | DP is an artemisinin-combination therapy consisting of the artemisinin derivative dihydroartemisinin and the bisquinoline piperaquine. This medication is taken on a monthly basis. Dihydroartemisinin-Piperaquine (DP): 3) The weight-based dosing of tablets of 40/320mg of DP is described below: Weight (kg) No. of 40/320mg tabs DP daily for 3 days ≤ 5 ¼ 6-10 ½ 11-14 ¾ 15-19 1 20-23 1 ¼ 24-25 1 ½ | 1 | 82 | 19 | 82 | 0 | 0 |
| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
Not provided
Not provided
| D000096724 |
| Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D013424 | Sulfanilamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |